COL12A1 encodes the alpha 1 chain of type XII collagen, a fibril-associated collagen with interrupted triple helices (FACIT) that plays a critical role in extracellular matrix organization and muscle function. Type XII collagen interacts with type I collagen-containing fibrils, where the COL1 domain associates with fibril surfaces while COL2 and NC3 domains localize in the perifibrillar matrix 1. The protein regulates collagen type I organization, creating structural frameworks that influence tissue mechanics and cellular behavior 1. Pathogenic variants in COL12A1 cause hereditary connective tissue disorders including Ullrich congenital muscular dystrophy 2 (recessive inheritance) and Bethlem myopathy 2 (dominant inheritance) 23. These conditions present with muscle weakness, joint hypermobility, and respiratory complications, ranging from severe neonatal hypotonia with respiratory failure to progressive muscular dystrophy 23. Molecular dynamics studies suggest that pathogenic variants destabilize the collagen XII trimer structure 2. Beyond muscle disorders, COL12A1 has emerging roles in cancer biology, where cancer-associated fibroblasts secrete collagen XII to alter collagen I organization, creating pro-invasive microenvironments that support metastatic dissemination in breast cancer 1. The gene is also implicated in satellite cell dysfunction, contributing to impaired muscle regeneration in neuromuscular disorders 4.