COL15A1 encodes collagen type XV alpha-1 chain, a FACIT collagen family member with multifaceted biological roles. As a structural component of the extracellular matrix and basement membranes, COL15A1 contributes to extracellular matrix organization and tensile strength 1. The encoded protein, restin, potently inhibits angiogenesis and possesses anti-tumoral properties 2. In normal physiology, COL15A1 expression marks distinct endothelial cell populations in the lung, specifically identifying systemic-venous endothelial cells localized to airways and visceral pleura 3. Regarding disease relevance, downregulation of COL15A1 is associated with reduced sarcopenia risk and improved muscle phenotypes, including higher appendicular lean mass and grip strength 4. In developmental pathology, expanded COL15A1-expressing systemic bronchial endothelial cells appear in FOXF1-deficient alveolar capillary dysplasia, correlating with microvascular loss 5. During pathological extracellular matrix remodeling, premetastatic lungs show decreased COL15A1 levels, suggesting involvement in cancer-associated tissue remodeling 6. In degenerative disc disease, COL15A1 is highly expressed in fibrochondrocytes associated with nucleus pulposus degeneration 7. At the mechanistic level, COL15A1 interacts with P4HB to regulate hepatocellular carcinoma cell growth and malignancy 2. Collectively, COL15A1 functions in vascular biology, extracellular matrix homeostasis, and tumor regulation, with therapeutic potential as a sarcopenia target.