COL5A3 encodes the alpha-3 chain of type V collagen, a minor fibrillar collagen component distributed throughout connective tissues that functions as an extracellular matrix structural constituent conferring tensile strength 1. Its expression is regulated by the transcription factor CBF/NF-Y binding to the core promoter region, with additional repressor proteins modulating gene activity 1. COL5A3 plays roles in multiple physiological processes. In skin and musculoskeletal development, it contributes to collagen fibril organization and extracellular matrix assembly 2. In inflammatory arthritis, COL5A3 is expressed by fibroblast subsets involved in extracellular matrix remodeling 2. The gene interacts functionally with MMP9 in eczema susceptibility, with MMP9-mediated degradation of COL5A3 influencing disease risk 3. Clinically, COL5A3 dysregulation associates with cancer progression. The gene is upregulated in high-grade serous ovarian cancer metastases 4 and in glioblastoma-influenced endothelial cells, correlating with patient survival outcomes 5. A six-gene signature incorporating COL5A3 predicts prostate cancer prognosis 6. Additionally, COL5A3 knockdown increases lipid accumulation in adipose tissue, suggesting roles in metabolic regulation 7. COL5A3 shows differential methylation in autism spectrum disorder 8, indicating potential neurodevelopmental relevance.