IGFALS encodes the acid-labile subunit (ALS), a leucine-rich glycoprotein essential for regulating insulin-like growth factor (IGF) bioavailability and transport 1. ALS forms stable ternary complexes with IGF-1 or IGF-2 and IGF-binding proteins (IGFBP-3 or IGFBP-5), creating a circulating reservoir that prolongs IGF half-lives and prevents potentially hypoglycemic effects of unbound IGFs 21. Primarily synthesized by hepatocytes, ALS expression is induced by growth hormone and suppressed by IL-1β 1. IGFALS mutations cause acid-labile subunit deficiency, resulting in modest growth retardation, pubertal delay, decreased osteogenesis, and enhanced adipogenesis 1. Gene dosage effects demonstrate that heterozygous carriers often exhibit reduced height, IGF-1, and IGFBP-3 levels compared to wild-type relatives 34. Clinical significance includes its role in idiopathic short stature diagnosis, where pathogenic variants contribute to growth restriction 35. Additionally, IGFALS functions as a tumor suppressor in hepatocellular carcinoma by stabilizing PPAR-γ through deubiquitination mechanisms 2. The protein's involvement extends beyond growth regulation, as demonstrated by its restoration of circulating IGF-1 levels in spinal muscular atrophy treatment models 6.