COL5A2 encodes the alpha-2 chain of type V collagen, a fibrillar collagen that serves as a minor but critical connective tissue component with widespread distribution 1. Type V collagen functions as a key determinant in tissue-specific matrix assembly and binds multiple molecules including DNA, heparan sulfate, thrombospondin, and heparin. It provides extracellular matrix structural integrity conferring tensile strength and participates in collagen fibril organization [GO annotations]. COL5A2 is prominently associated with classic Ehlers-Danlos syndrome, where approximately 50% of patients harbor mutations in COL5A1 or COL5A2, typically resulting in haploinsufficiency or production of functionally defective type V collagen 1. Beyond connective tissue disorders, COL5A2 emerges as a disease-relevant gene in multiple pathologies: it is upregulated in gastric cancer and correlates with poor prognosis and reduced immunotherapy benefit 2; functions as a cancer-associated fibroblast biomarker in ovarian cancer with prognostic significance 3; is elevated in endometrial fibrosis associated with intrauterine adhesions 4; is stress-responsive in aortic smooth muscle cells protecting against aneurysm and dissection 5; and is upregulated in cerebral aneurysm tissue and calcific aortic valve disease 67. These findings highlight COL5A2's critical role in both physiological matrix homeostasis and pathological fibrotic and vascular remodeling processes.