Livestock growth is a fundamental aspect of the livestock industry and plays a major role in determining production efficiency and economic profitability [1]. Growth-related traits, including body weight, feed intake, and body conformation, are closely associated with production performance, particularly in meat-producing livestock species [2]. Improvement of these traits not only increases the economic value of livestock but also enhances feed utilization efficiency and supports sustainable production systems [3].

Genetic factors play a crucial role in determining individual variation in growth traits. Several candidate genes have been reported to be strongly associated with growth characteristics, including growth hormone (GH), growth hormone receptor (GHR), myostatin (MSTN), and insulin-like growth factor 2 (IGF2) [4, 5]. These genes regulate important biological processes such as metabolism, cell differentiation, muscle development, and feed conversion efficiency into body mass [6]. However, the expression of growth traits is not determined solely by genetic background, but is also influenced by environmental conditions, nutritional status, management practices, and the physiological health of livestock [7]. Animals with superior genetic potential may fail to achieve optimal growth performance if adequate nutrition and proper husbandry practices are not provided. Therefore, effective breeding programs require an integrated approach combining genetic improvement with optimized nutritional strategies and environmental management to maximize growth potential and production efficiency [8].

Improved livestock production and growth efficiency are often associated with the insulin-like growth factor (IGF) system through nutrition, genetic selection, or the application of growth-promoting strategies [9]. For example, increased IGF1 levels have been shown to enhance growth rate and feed efficiency in beef cattle and poultry [10]. IGF1 and IGF2 play essential roles in regulating cell proliferation and differentiation, particularly in muscle, bone, and vital organ tissues. IGF2 acts as a major mediator of GH activity and functions through systemic, paracrine, and autocrine mechanisms within body tissues [11]. Because of its central role in regulating growth and metabolism, IGF2 has become an important research target for improving livestock productivity through natural and sustainable approaches [12].

The IGF2 gene is influenced not only by genetic factors but also by environmental conditions such as nutrition, farm management, and stress [13]. Animals with superior genetic potential typically show faster growth rates and better feed efficiency, whereas inadequate nutrition or stressful conditions, including feed restriction or disease exposure, may decrease IGF expression and hinder growth performance [14]. Regulation of IGF2 expression involves complex interactions among genetic variation, nutritional status, epigenetic modifications, and regulatory pathways across different livestock species [15]. Although many studies have explored the role of IGF2 in individual species or specific conditions, a comprehensive overview combining genetic polymorphisms, nutritional regulation, epigenetic control, and biotechnological applications of IGF2 across livestock species remains limited [16].

Therefore, this review compiles and compares current evidence on IGF2-mediated growth regulation, with particular focus on muscle development, feed efficiency, carcass quality, and responses to nutritional and environmental stress [17]. Identifying favorable IGF2 promoter variants may provide valuable markers for selective breeding programs aimed at improving livestock productivity and efficiency [18].

Despite extensive research on growth-related genes in livestock, understanding of the role of IGF2 in regulating growth performance, metabolic efficiency, and carcass quality remains incomplete. Most studies focus on individual species, specific polymorphisms, or isolated physiological functions, without offering a comprehensive framework that integrates genetic, nutritional, epigenetic, and biotechnological regulation of IGF2. Many reports examine the interaction between IGF2 and other growth-related genes such as GH, GHR, and MSTN separately, while the coordinated regulation of these genes under different nutritional and environmental conditions has not been sufficiently summarized. Additionally, although IGF2 polymorphisms have been linked to economically important traits, applying these findings in marker-assisted selection, genomic selection, and precision breeding programs remains inconsistent across livestock species.

Another limitation in the current literature is the lack of integrated evaluation of how nutritional status, stress, management practices, and epigenetic mechanisms influence IGF2 expression and its downstream signaling pathways. Previous studies have demonstrated that feed composition, energy balance, and environmental stress can modify the activity of the insulin-like growth factor axis, but the combined effects of these factors on IGF2-mediated growth regulation have not been systematically reviewed. In addition, recent advances in biotechnology, including genome editing, transcriptomic analysis, and epigenetic modulation, have provided new opportunities to regulate IGF2 expression; however, the potential benefits, limitations, and welfare implications of these approaches have not been critically synthesized in a single review. Therefore, a comprehensive evaluation that connects molecular mechanisms with practical applications in livestock production is still required.

Therefore, the present review aims to provide a comprehensive and integrative overview of the role of IGF2 as a central regulator of growth, muscle development, nutrient metabolism, and production efficiency in livestock. This review summarizes current knowledge on the molecular functions of IGF2, its interaction with other growth-related genes such as GH, GHR, and MSTN, and its involvement in major signaling pathways controlling cell proliferation, differentiation, and protein synthesis. In addition, this review evaluates the influence of genetic polymorphisms, nutritional factors, environmental conditions, and epigenetic regulation on IGF2 expression across different livestock species.

The review also aims to compile recent findings on the use of IGF2 in marker-assisted selection, genomic selection, and modern biotechnological methods, including genome editing and epigenetic modulation, for enhancing growth performance and feed efficiency while safeguarding animal health and welfare. By combining information from molecular biology, animal nutrition, genetics, and biotechnology, this review strives to provide a solid scientific basis for using IGF2 as a key target in sustainable and precision livestock production systems. Ultimately, this synthesis is expected to support future research and breeding strategies focused on improving productivity, product quality, and economic efficiency in modern livestock industries.

The IGF2 gene is a key regulator of muscle growth and metabolism in cattle, pigs, sheep, and chickens. Extensive evidence demonstrates that elevated IGF2 expression is positively associated with enhanced protein synthesis and myoblast proliferation, leading to increased muscle accretion and an improved M/F ratio [39]. Consequently, IGF2 has been widely recognized as a major genetic determinant of carcass quality traits across multiple livestock species [40]. Mutations in the IGF2 regulatory region can significantly increase muscle growth while reducing subcutaneous fat content [41]. For example, specific mutations in IGF2 are associated with a 15%–20% reduction in back-fat thickness without compromising meat quality in pigs [42]. Similarly, IGF2 gene polymorphisms in cattle have been correlated with economically important traits such as marbling, meat tenderness, and feed efficiency. These findings underscore the potential of IGF2-based genetic selection strategies to enhance meat production quality and quantity in livestock populations [43].

IGF2 plays a role not only in muscle growth but also in energy metabolism and body composition regulation. The IGF2 hormone produced by this gene exerts a strong anabolic effect, aiding in increasing the efficiency of feed conversion into muscle mass [44]. IGF2 is a key growth factor involved in the proliferation and differentiation of muscle, bone, and internal organs [45]. It remains active in supporting hypertrophy by activating the PI3K/AKT/mTOR signaling pathway, which boosts protein synthesis and muscle growth. Additionally, IGF2 interacts with transcription factors such as Myogenin and MyoD, which are involved in controlling muscle cell differentiation and maturation [46].

Moreover, the IGF2 gene plays a key role in muscle growth, cell differentiation, and energy metabolism, making it a prime candidate as a molecular marker for livestock meat production. IGF2 increases protein synthesis and muscle cell proliferation, thereby directly influencing the meat-to-fat ratio and carcass quality [47]. Numerous quantitative genetic studies have linked IGF2 to QTLs associated with growth performance, feed efficiency, and carcass characteristics. The identification of a quantitative trait nucleotide (QTN) within the IGF2 regulatory element has provided critical insights into how subtle genetic variations can induce substantial changes in gene expression and phenotypic outcomes [48]. The QTN in the IGF2 regulatory element was discovered through genome-wide association studies and QTL mapping, which aimed to link genetic variation to livestock production performance. This mutation is located in the regulatory region of IGF2 expression, which controls gene transcription levels in various tissues [49] (Figure 1).

Mutations in this region influence gene expression by altering interactions with transcription factors and epigenetic mechanisms, including DNA methylation and histone modifications [50]. The discovery of QTN mutations in IGF2 offers significant benefits in GS and MAS-based breeding [51]. Breeders can select individuals with favorable IGF2 alleles using genetic data to improve growth efficiency, carcass quality, and the balance between muscle and fat mass. Cattle carrying beneficial IGF2 mutations exhibit improved feed conversion and endurance, making them a prime target in modern breeding programs [52]. Livestock carrying advantageous IGF2 variants consistently exhibit enhanced muscle hypertrophy, increased daily weight gain, and superior feed conversion efficiency. These animals can utilize nutrients more effectively, achieving accelerated growth rates without disproportionate increases in feed intake [53]. Collectively, these attributes position IGF2 as a central genetic target in modern livestock breeding programs aimed at optimizing meat production and economic efficiency [54].

The IGF2 gene is a crucial growth factor that plays a central role in regulating nutrient metabolism in livestock. As a peptide hormone, IGF2 is involved not only in growth and development but also in energy metabolism and nutrient use [73]. A thorough understanding of the molecular mechanisms through which IGF2 influences nutrient metabolism is vital for enhancing livestock productivity via integrated nutritional and genetic strategies [74]. This highlights IGF2 as a key factor in boosting livestock growth and efficiency. Higher IGF2 expression is linked to increased body weight and lean muscle mass. Therefore, genetic selection targeting IGF2 could be an effective strategy to improve high-quality meat production in livestock [75].

IGF2 regulation is also closely linked to feed efficiency and nutrient utilization. This factor enhances the use of amino acids and glucose in cells, supporting more efficient growth [76]. Manipulating IGF2 expression through targeted nutritional strategies offers a practical way to improve feed efficiency while also decreasing nitrogen waste and reducing environmental impact. Optimizing IGF2 activity could thus be a sustainable method to boost livestock production and lessen the environmental footprint [77]. Since IGF2 plays a key role in managing nutrient metabolism, there is considerable potential to enhance livestock productivity through genetic selection combined with nutritional management [78]. Interactions among IGF2 and environmental, nutritional, and genetic factors provide valuable insights into the regulation of growth and metabolic efficiency in livestock [79]. At the cellular level, IGF2 influences metabolism via complex signaling pathways that coordinate nutrient use, improve feed conversion, and regulate protein synthesis and breakdown [80].

One of the main functions of IGF2 in nutrient metabolism is to promote protein synthesis and reduce muscle protein breakdown. This process is essential for supporting livestock growth, especially during rearing and fattening stages [81]. IGF2 works together with other growth hormones, such as IGF1 and insulin, to enhance amino acid uptake and encourage muscle fiber development, highlighting its potential as a genetic target for boosting meat production efficiency [82]. Besides its role in protein metabolism, IGF2 also significantly affects energy metabolism and glucose use. It increases insulin sensitivity, which speeds up glucose absorption and storage in muscle and liver tissues [83]. This improves how efficiently energy from feed is used, directly impacting growth and overall health [84]. Higher IGF2 levels may also decrease the need for fat tissue as an energy source, allowing more dietary energy to be used for muscle building [85].

Integration of IGF2-targeted genetic selection with optimized nutritional strategies offers a strong approach for improving livestock production efficiency and sustainability [86]. The IGF2 gene plays a crucial role in regulating nutrient metabolism in livestock by acting as a key mediator in metabolic pathways influencing muscle growth, protein synthesis, and feed conversion efficiency [87]. IGF2 stimulates cellular proliferation and differentiation through interaction with specific receptors, particularly in skeletal muscle and metabolically active organs such as the liver and pancreas. In addition to protein metabolism, IGF2 influences energy metabolism, especially glucose and lipid utilization [88]. IGF2 increases insulin sensitivity, allowing muscle cells to absorb and utilize glucose more efficiently, thereby reducing excessive fat accumulation and directing more energy toward muscle growth [89]. Appropriate nutritional strategies, including balanced carbohydrate and protein formulation, can maximize IGF2 expression and improve production efficiency [90]. Overall, understanding the mechanisms by which IGF2 regulates nutrient metabolism provides important opportunities to improve livestock productivity through scientifically based nutritional and genetic interventions [91]. Interaction between metabolic pathways and IGF2 represents an important strategy to optimize growth, increase feed efficiency, and produce higher-quality livestock products [92].

The IGF2 gene plays a crucial role in regulating growth, metabolism, and reproductive performance in livestock, particularly poultry. Polymorphisms in the IGF2 gene, especially single-nucleotide polymorphisms (SNPs), have been identified as potential markers of reproductive traits in poultry [93]. Variations in regulatory regions, such as promoter and intronic regions, can influence IGF2 expression. These genetic variations provide valuable information for marker-assisted selection (MAS), enabling breeders to selectively improve production efficiency [94]. Multiple IGF2 polymorphisms exert substantial effects on meat production traits across livestock species. For example, in the swine industry, specific mutations in the IGF2 regulatory region have been associated with increased muscle growth and decreased back-fat deposition, resulting in more efficient carcasses [95].

IGF2 also affects follicular development, hormone secretion, and overall reproductive success in poultry. This gene encourages cell growth and specialization and helps maintain healthy ovarian tissue function, which is vital for egg production [96]. Recent research has found specific IGF2 SNP linked to increased egg production, better eggshell quality, and longer reproductive lifespan in poultry [97]. These polymorphisms assist in identifying livestock with superior genetic traits, making them useful markers for selective breeding programs [98].

Mapping IGF2 polymorphisms can be used in genome-based breeding to produce livestock with better meat qualities. IGF2 activates the PI3K/AKT/mTOR signaling pathway by binding to the IGF1R receptor, which stimulates protein synthesis and muscle growth [99]. Additionally, IGF2 interacts with IGF-binding proteins (IGFBPs), which regulate its bioavailability and tissue-specific activity. Functional genomics and transcriptomic methods offer powerful tools for understanding how specific SNPs affect IGF2 expression, signaling efficiency, and reproductive physiology [100].

Polymorphisms in the IGF2 gene influence various biological functions, especially those related to reproductive traits in poultry. Genetic variations, including SNPs, can change gene expression and function [101]. Specific IGF2 polymorphisms have been linked to higher egg-laying rates, better eggshell quality, and a longer reproductive period [102]. Certain SNPs can boost IGF2 expression in ovarian tissue, promoting follicular development and increasing ovulation frequency [103]. Identifying and understanding these polymorphisms enable breeders to use genetic selection to improve reproductive traits like egg size and production efficiency [104].

Although current research emphasizes the potential of IGF2 polymorphisms to enhance egg production traits, many aspects still need exploration. Future studies should examine broader genetic and environmental interactions that influence IGF2 expression and its role in reproductive performance [105]. Investigating the interactions between IGF2 and genes involved in steroid hormone synthesis or yolk formation could provide deeper insights into the genetic networks controlling egg-laying efficiency [106]. The important role of IGF2 in avian reproductive physiology further underscores its potential to improve productivity through polymorphisms [107]. IGF2 polymorphisms are also linked to variations in body size and growth, with some allelic variants being beneficial for faster growth and better feed efficiency [108]. Therefore, IGF2 functions not only as a regulator of growth and reproduction but also as an essential genetic factor in overall production performance [109]. Overall, these findings suggest that IGF2 is a promising molecular target for MAS aimed at improving key traits in modern poultry breeding programs [110].

Genetic engineering is an innovative approach to increase IGF2 expression to boost livestock growth efficiency and nutrient metabolism [111]. Because of the central role of IGF2 in regulating muscle development, energy metabolism, and feed conversion efficiency, targeted manipulation of its expression can significantly enhance livestock productivity [112]. Modern genetic engineering methods allow precise control of IGF2 through genome editing technologies such as CRISPR–Cas9, epigenetic regulation, and transgenic approaches [113]. In various livestock species, increasing IGF2 expression via CRISPR–Cas9 has been shown to promote muscle growth, improving carcass quality and meat production [114].

In addition to CRISPR–Cas9 techniques, epigenetic approaches are also promising for modifying IGF2 expression [115]. Epigenetic manipulation through nutritional input or molecular intervention can naturally increase IGF2 expression, allowing livestock to grow faster and more efficiently without permanent genetic modification [116]. This approach is considered safer and more widely applicable in the livestock industry because regulatory restrictions are less strict than those for conventional genetic engineering technologies [117]. With advances in molecular technologies, modifying IGF2 expression has become a strategic method for improving livestock productivity. Genetic engineering has thus become an important tool for enhancing IGF2 activity to support growth and metabolic efficiency [118]. One major advantage of increasing IGF2 expression through CRISPR–Cas9 is optimizing carcass composition, where more nutrients are directed toward muscle growth rather than fat deposition [119]. The meat-to-fat ratio is a key factor in determining product quality and market value in the livestock industry. Therefore, improving IGF2 activity not only boosts production efficiency but also meets consumer demand for healthier and higher-quality products [120].

Beyond CRISPR–Cas9 and traditional transgenic methods, a wide array of molecular and genomic technologies has been used to modify IGF2 activity in livestock species (Table 1) [121–129]. These approaches work at various regulatory levels, from gene silencing to genome editing and advanced selection tools, showcasing the versatility of IGF2 as a biotechnology target.

refer to the specific genetic element modified or selected (e.g., coding region, regulatory region, or transcript). Observation outcomes summarize the primary reported benefit related to muscle growth, meat production, or related traits. References correspond to the numbered list provided in the manuscript. Abbreviations: CRISPR/Cas9 = clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9, GWAS = genome-wide association study, ICR = imprinting control region, IGF2 = insulin-like growth factor 2, miRNA = microRNA, SNP = single-nucleotide polymorphism.

RNA interference (RNAi) represents one of the earliest functional genomic tools used to investigate the regulation of IGF2. Targeted suppression of IGF2 mRNA through RNAi has clarified its role in muscle growth regulation and developmental signaling pathways in chickens [121]. Although RNAi mainly serves as a research tool, it provides important mechanistic insight into IGF2-mediated anabolic processes.

Genome editing with CRISPR/Cas9 allows precise and permanent changes to the IGF2 gene. In pigs, editing exon-1 directly has led to increased muscle mass and better feed efficiency, stressing the economic value of IGF2-focused techniques in commercial swine farming [122]. Besides direct editing, MAS has been used in cattle by identifying advantageous IGF2 SNPs, which correlate with higher body weight, improved carcass traits, and increased gene activity [123].

Epigenetic modification further broadens the possibilities for IGF2 regulation without changing the DNA sequence. In sheep, methylation and demethylation of the imprinting control region activate IGF2 expression, showing how epigenomic remodeling can impact muscle development and growth traits [124]. Similarly, transgenic methods involving the insertion of additional IGF2 gene copies in goats have led to faster and more consistent muscle growth, confirming the anabolic role of sustained IGF2 overexpression [125].

At the transcriptional level, promoter engineering has been utilized in cattle to increase IGF2 expression [126]. Synthetic mRNA therapy has also become a temporary and reversible approach, where administering artificial IGF2 mRNA to chicken speeds up early growth without causing permanent changes to the genome [127].

Genomic selection approaches also contribute to optimization of IGF2. Genome-wide association studies in pigs have identified intronic SNPs associated with increased IGF2 activity and enhanced muscle growth [128]. Post-transcriptional regulation through microRNA modulation has also been reported, where inhibition of miR-675 improves IGF2 mRNA stability and translation efficiency, thereby promoting muscle accretion [129].

In addition to production benefits, modulation of IGF2 expression can also enhance livestock health and welfare [130]. Excessive fat buildup is often linked to metabolic disorders, lower endurance, and higher mortality rates [131]. Proper regulation of IGF2 may help livestock achieve healthier body composition, better endurance, and higher-quality meat [132]. This approach can also promote more stable large-scale production, boosting the global competitiveness of the livestock industry [133]. Overall, CRISPR–Cas9, epigenetic modulation, and integrated biotechnological strategies targeting IGF2 offer a strong framework for improving meat production efficiency without sacrificing animal health or product quality [134]. When combined with optimized nutrition and management, IGF2-based interventions are a promising way to achieve sustainable, competitive, and cost-effective livestock production systems [135].

IGFs, especially IGF1 and IGF2, are peptide hormones that control growth, development, and metabolism in livestock [136]. These hormones serve as key mediators of GH activity and are structurally similar to insulin. While IGF1 is mainly produced in the liver in response to GH stimulation, IGF2 plays a more significant role in fetal and early postnatal development, influencing long-term growth potential and metabolic programming [137]. IGFs act through specific receptors, mainly IGF1R, to promote cell proliferation, differentiation, and survival in various tissues. Their production and activity are affected by various physiological and environmental factors, including nutritional status, GH levels, and stress [138]. IGF1 production is regulated by the GH–IGF axis via complex feedback mechanisms that maintain growth homeostasis. Additionally, IGFs have autocrine and paracrine actions that regulate local growth in tissues such as skeletal muscle, bone, and adipose tissue [139]. Disruption of this system can noticeably impact growth performance and metabolic efficiency in animals. The biological activity of IGFs is strongly affected by six types of binding proteins called insulin-like growth factor-binding proteins (IGFBPs) [140]. These IGFBPs refine IGF signaling and influence tissue-specific growth responses and metabolic regulation through these mechanisms [141].

Experimental evidence from both in vivo and in vitro studies further substantiates the functional importance of IGF2 in regulating growth performance and metabolic activity in livestock species (Table 2) [142–149]. In vivo investigations demonstrate that modulation of IGF2 expression directly influences productive traits and tissue development. In transgenic pigs, elevated IGF2 expression has been associated with improved feed conversion ratio (FCR) and enhanced meat aging quality, supported by carcass evaluation, real-time quantitative polymerase chain reaction (RT-qPCR), and muscle histology findings [142]. Similarly, studies in layer chickens have shown that IGF2 expression during early developmental stages contributes to optimal digestive tract growth, indicating its role in organogenesis and nutrient absorption capacity [143]. In dairy cows, IGF2 expression has been positively correlated with energy balance status and milk production, where higher expression levels were observed under positive energy conditions, accompanied by improved lactational performance and metabolic indicators [144].

In vivo studies were conducted in live animals; in vitro studies used primary or immortalized cell cultures. Research purposes indicate the main objective(s) of each study as described in the original publication. Results represent the key findings directly related to IGF2 function, growth, metabolism, or meat/milk quality. Research methods include the primary techniques used for gene expression, protein analysis, or histological evaluation. Figure 1 (goat liver cell culture and porcine embryo fibroblast cells) is referenced where applicable to illustrate specific in vitro outcomes. References correspond to the numbered list provided in the manuscript. Abbreviations: FCR = feed conversion ratio, GLUT4 = glucose transporter type 4, IGF2 = insulin-like growth factor 2, MTT = 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, PI3K = phosphoinositide 3-kinase, RT-qPCR = reverse transcription quantitative polymerase chain reaction.

Complementary in vitro studies provide mechanistic insights into molecular pathways regulated by IGF2. Stimulation by IGF2 activates the PI3K–AKT–mTOR signaling pathway in chicken muscle cell cultures, accelerating muscle protein synthesis and promoting anabolic activity, as confirmed by Western blot, RT-qPCR, and immunofluorescence analyses [145]. In goat hepatocyte cultures, IGF2 regulates lipid metabolism by reducing intracellular lipid accumulation, suggesting its involvement in hepatic energy homeostasis [146]. Moreover, IGF2 enhances myogenic differentiation in duck muscle progenitor cells, increasing myotube formation and reinforcing its role in skeletal muscle development [147]. Similar proliferative and anabolic effects have been observed in bovine myoblast cultures, where IGF2 stimulation increases cell proliferation and protein synthesis [148]. IGF2 also upregulates downstream metabolic genes within the PI3K/AKT pathway and increases GLUT4 expression in porcine embryo fibroblast cells, highlighting its role in glucose uptake and metabolic efficiency [149].

Increased IGF2 expression has been positively linked to greater muscle mass, better feed efficiency, and faster growth rates in pigs, cattle, and poultry [150]. Targeted modulation of IGF2 expression offers a promising strategy to boost lean meat production without harming animal health or welfare [151]. Regulation of IGF2 helps improve carcass quality, and higher IGF2 activity is generally tied to more efficient nutrient use [152]. Mutations and polymorphisms in the IGF2 gene have been associated with increased body weight and muscle growth in livestock. A well-known example is a mutation within the IGF2 regulatory element that causes elevated muscle-specific expression, resulting in enhanced muscle development and better carcass traits [153]. Advances in genomic selection technology enable breeders to find animals with favorable IGF2 variants for use in breeding programs aimed at achieving optimal growth and improved feed efficiency [154]. However, interactions between genetic background and environmental factors, including nutrition, management practices, and overall husbandry conditions, strongly influence how IGF2 is expressed phenotypically [155]. As a molecular link between genetics and the endocrine system, the IGF2 gene affects hormonal balance and metabolic efficiency. The IGF2 gene also plays a role in the insulin signaling pathway that controls glucose uptake, protein synthesis, and energy partitioning, helping to optimize animal performance under varying environmental and nutritional conditions [156]. Incorporating IGF2 expression analysis into livestock selection programs can aid in predicting superior breeds and enhancing understanding of animal resilience, adaptability, and long-term production potential [157].

Changes in IGF2 expression can also affect the overall health and welfare of animals [158]. Although IGF2 plays a central role in regulating muscle development and energy metabolism, dysregulation of its expression may disrupt metabolic homeostasis and increase the risk of adverse health outcomes [159]. Imbalance in IGF2 signaling can affect coordination between muscle accretion and lipid metabolism, potentially leading to metabolic disorders [160]. The IGF2 gene can also influence the endocrine system, particularly in interaction with other growth-related hormones such as insulin and IGF1. The IGF2 gene interacts with insulin to regulate glucose utilization in the body, and increased IGF2 expression may alter blood glucose regulation [161]. Understanding the complex interactions between IGF2 and other hormones is essential to prevent negative effects on animal health. Changes in IGF2 expression may also influence animal behavior in addition to physical effects [162]. Alterations in metabolic processes and hormonal balance can affect both mental and physical well-being. Stress caused by rapid muscle growth or disturbances in energy metabolism can reduce quality of life, weaken the immune system, and increase susceptibility to disease [163].

Growth-related hormones, including IGF2, influence immune cell function, and changes in IGF2 levels can impact the body’s ability to respond to infection or stress [164]. Excessive IGF2 expression may hinder optimal immune responses, increasing vulnerability to infection and disease [165]. While animals might stay healthy after genetic modification, monitoring hormonal balance and its effects on immune function remains essential. Increasing IGF2 expression benefits meat production efficiency; however, potential side effects, especially those involving hormonal balance, need careful assessment [166]. Investigating hormonal interactions and the long-term effects of IGF2 genetic modification is crucial to identify potential health risks [167].

Biotechnological modification of IGF2 expression through genetic engineering has shown significant potential for enhancing livestock productivity [168]. However, maintaining physiological balance is essential for animal welfare. Uncontrolled alterations in IGF2 expression can disrupt metabolic stability, for example by causing insulin problems or increased blood glucose levels that may lead to insulin resistance [169]. Excessive IGF2 activity might also worsen metabolic disorders, including obesity-related issues, thereby decreasing productivity and harming animal health [170]. Therefore, strategies involving genetics and biotechnology targeting IGF2 should be applied within a carefully regulated framework that considers animal health, welfare, and production objectives [171].

The present review highlights the central role of IGF2 as a key molecular regulator of growth, muscle development, metabolic efficiency, and overall production performance in livestock. Evidence collected from genetic, nutritional, physiological, and biotechnological studies consistently demonstrates that IGF2 significantly influences economically important traits, including body weight gain, muscle fiber formation, carcass quality, feed conversion efficiency, reproductive performance, and metabolic regulation. Experimental findings from both in vivo and in vitro studies confirm that modulation of IGF2 expression affects major signaling pathways such as PI3K–AKT–mTOR, which regulate protein synthesis, cell proliferation, and energy utilization. Polymorphisms within the IGF2 gene, particularly in regulatory regions, have been strongly associated with improved growth traits in cattle, pigs, poultry, and small ruminants, supporting its application as a reliable candidate gene for MAS and genomic selection programs. In addition, recent advances in biotechnology, including CRISPR–Cas9 genome editing, epigenetic modulation, and transcriptomic approaches, have provided new opportunities to regulate IGF2 expression to enhance livestock productivity while maintaining desirable carcass characteristics.

From a practical standpoint, combining IGF2-based genetic selection with optimized nutritional management and improved husbandry practices presents a promising approach to increasing livestock production efficiency sustainably. Animals with advantageous IGF2 variants typically show faster growth, better feed efficiency, and enhanced meat quality, which can directly boost farm profitability and industry competitiveness. Additionally, understanding how IGF2 expression interacts with environmental factors such as diet, stress, and management conditions enables the development of precision breeding and feeding strategies tailored to specific production systems. These methods can lead to more efficient resource use, lower production costs, and higher product quality, supporting the long-term sustainability of the livestock industry.

One of the major strengths of the current review is the integration of information from multiple disciplines, including molecular genetics, animal nutrition, physiology, and biotechnology, providing a comprehensive understanding of IGF2-mediated growth regulation across different livestock species. However, several limitations remain. Many studies have been conducted in specific species or under controlled experimental conditions, which may limit the direct application of the results to diverse production environments. In addition, the long-term effects of manipulating IGF2 expression, particularly through genetic engineering and epigenetic modification, are not yet fully understood and require careful evaluation to ensure animal health, welfare, and consumer acceptance.

Future research should emphasize large-scale multi-species studies to clarify how IGF2 polymorphisms, nutritional factors, and environmental conditions interact within practical farming systems. Additional research is also necessary to understand the epigenetic regulation of IGF2, its interactions with other growth-related genes such as GH, GHR, and MSTN, and its role in immune function and metabolic stability. Developing safe and ethically acceptable biotechnological methods for controlling IGF2 expression will be crucial for successfully applying this gene in modern breeding programs.

In conclusion, IGF2 is a key molecular target that connects genetics, nutrition, and physiology in livestock production. Strategic use of IGF2 through selective breeding, nutritional adjustments, and controlled biotechnological methods has strong potential to enhance growth, improve production efficiency, and boost product quality while safeguarding animal health and welfare. Ongoing research that combines molecular biology with practical livestock management is crucial to fully harness the benefits of IGF2 for sustainable and economically viable animal production systems.

SRA, SS, MAA, ARK, ML, and EJK: Contributed to the literature search, conceptualization, and initial drafting of the manuscript. ML, MAA, RZA, WW, ZNAR, SRA, and SHW: Critical revision and substantive editing of the manuscript for important intellectual content. MAA, WW, WPL, RZA, and TRF: Manuscript drafting and subsequent revisions. MS, WW, RR, WPL, SRA, RZA, and ARK: Managed reference organization, formatting, and verification. All authors have read and approved the final version of the manuscript and agree to be accountable for all aspects of the work.