COL22A1 encodes collagen type XXII, a fibril-associated collagen that serves multiple physiological roles. In skin, COL22A1 acts as a cell adhesion ligand for epithelial cells and fibroblasts 1, and is a TGFβ early response gene mediating fibroblast-to-myofibroblast transition in systemic sclerosis 1. COL22A1 is critical for vascular integrity; zebrafish loss-of-function studies demonstrate that COL22A1 maintains vascular stability, with homozygous mutants exhibiting increased intracranial hemorrhages and vascular permeability 2. A human COL22A1 variant (E736D) segregates with familial intracranial aneurysms and impairs protein secretion, suggesting COL22A1 mutations are risk factors for vascular disease 2. Genome-wide association studies identified COL22A1 polymorphisms associated with serum creatinine levels, indicating a role in kidney function regulation 3. In pathological contexts, COL22A1 is upregulated in glioblastoma and correlates with poor prognosis, immune infiltration, and tumor progression 456. Functionally, COL22A1 silencing in glioma cells impairs proliferation, migration, and invasion 6. Conversely, COL22A1 SNPs showed no association with anterior cruciate ligament rupture risk in athletes 7. COL22A1 represents an emerging therapeutic target in fibrotic and neoplastic diseases.