COL16A1 encodes collagen type XVI alpha 1 chain, a fibril-associated collagen with interrupted triple helices (FACIT) that plays crucial roles in extracellular matrix organization and cell adhesion. The protein mediates cell attachment and induces integrin-mediated cellular reactions, including cell spreading and morphological alterations [UniProt]. COL16A1 is significantly upregulated in various pathological conditions, particularly fibrotic diseases. In keloids, COL16A1 is regulated by super-enhancers and associated with the core transcription factor FOXP1, contributing to anti-senescence mechanisms in fibrosis 1. The gene shows differential expression in tissue remodeling contexts, being enriched in high-flow regions of the trabecular meshwork compared to low-flow regions 2. COL16A1 expression is induced by inflammatory cytokines, as demonstrated by IL-17A promoting its expression in valvular endothelial cells, contributing to calcific aortic valve disease progression 3. Additionally, COL16A1 serves as a prognostic biomarker in cancer, being part of cancer-associated fibroblast signatures in ovarian cancer 4 and stemness-related prognostic signatures 5. The gene is also upregulated in severe intrauterine adhesions, where it is regulated by miR-543 6, suggesting its involvement in pathological tissue remodeling and fibrosis across multiple organ systems.