COL1A2 encodes the alpha-2 chain of type I collagen, a fibrillar collagen essential for structural integrity of connective tissues 1. Type I collagen comprises two alpha-1 chains and one alpha-2 chain that form triple helices conferring tensile strength to extracellular matrix 2. COL1A2 regulates osteoblast differentiation through histone lactylation-dependent mechanisms and functions in skeletal system development, skin morphogenesis, and blood vessel formation 3. Pathogenic COL1A2 mutations account for approximately 90% of osteogenesis imperfecta (OI) cases 14. Mutations causing qualitative defects (amino acid substitutions, particularly glycine substitutions) typically produce more severe phenotypes than quantitative mutations (null alleles) 5. COL1A2 variants also cause Ehlers-Danlos syndrome subtypes and OI-EDS overlap syndromes, with certain arginine-to-cysteine variants associated with vascular fragility 6. Genotype-phenotype correlations reveal N-terminal mutations are associated with absence of dentinogenesis imperfecta 5. Clinically, bisphosphonate therapy effectively reduces vertebral fractures in OI patients, though long-bone fractures remain frequent 1. Emerging evidence suggests COL1A2 expression in myofibroblasts contributes to pulmonary fibrosis pathogenesis and elevated expression correlates with gastric cancer progression 72.