COL1A1 encodes the alpha-1 chain of type I collagen, a fibrillar collagen that serves as a major structural component of the extracellular matrix, providing tensile strength to connective tissues 1. Type I collagen is essential for skeletal development, blood vessel formation, and maintains structural integrity across multiple tissues 2. Beyond its classical structural role, COL1A1+ endothelial cells regulate tumor progression through endothelial-to-mesenchymal transition, promoting gastric cancer invasiveness via the ANGPTL4-SDC4 axis 3. COL1A1 expression is also a key biomarker associated with osteoporosis and cartilage injury pathogenesis 4. Pathogenic COL1A1 variants cause multiple connective tissue disorders. Heterozygous variants account for approximately 48% of osteogenesis imperfecta (OI) cases in Indian populations, manifesting as recurrent fractures, blue sclerae, and dentinogenesis imperfecta 2. Missense variants, particularly glycine substitutions in the triple helix, are most common 2. COL1A1 mutations also cause Ehlers-Danlos syndrome subtypes and OI-EDS overlap syndromes, with certain variants conferring vascular fragility requiring specialized clinical surveillance 1. Additionally, a pathogenic COL1A1-PDGFB translocation characterizes dermatofibrosarcoma protuberans, a rare soft tissue sarcoma responsive to imatinib therapy 5. Pamidronate therapy improves bone density in moderate-to-severe OI, demonstrating clinical utility in managing COL1A1-related skeletal disease 2.