COL18A1 encodes collagen type XVIII alpha 1 chain, a heparan sulfate proteoglycan that serves as a crucial regulator of angiogenesis and vascular integrity. The protein functions as a potent inhibitor of endothelial cell proliferation and angiogenesis, potentially through binding to heparan sulfate proteoglycans involved in growth factor signaling 1. COL18A1 can be cleaved to generate endostatin, which inhibits angiogenesis by blocking VEGFA-mediated signaling and its interaction with VEGFR2 receptor 1. The protein is essential for blood-brain barrier integrity, as Col18a1 knockout mice exhibit elevated BBB permeability, microvascular damage, and neuroinflammation characteristic of cerebral small vessel disease 2. COL18A1 demonstrates tissue-specific expression patterns, with high expression during human adipocyte differentiation 3 and differential expression in cardiac adipose tissue depots 4. Mutations in COL18A1 cause Knobloch syndrome, characterized by early-onset retinal detachment and ocular abnormalities 56. Genetic variants in COL18A1 have also been associated with increased osteosarcoma risk and obesity susceptibility in type 2 diabetes patients 73.