COL28A1 encodes collagen type XXVIII alpha 1 chain, a structural extracellular matrix protein that functions as a cell-binding protein 1. COL28A1 participates in collagen fibril organization and provides tensile strength to extracellular matrix [GO annotations]. The protein is synthesized in the endoplasmic reticulum lumen and secreted to the extracellular region, where it contributes to skeletal system morphogenesis and tissue structural integrity 1. Mechanistically, COL28A1 overexpression promotes renal tubular epithelial cell proliferation and migration while enhancing epithelial-to-mesenchymal transition (EMT) induced by TGF-β1, suggesting roles in cell-matrix interactions and fibrotic responses 2. The protein forms interconnected collagen networks with other collagen types and interacts with extracellular matrix receptors 1. COL28A1 shows clinical relevance across multiple diseases. It is associated with complex neuropsychiatric disorders; genetic variants in COL28A1 are linked to intellectual disability and schizophrenia in oligogenic combinations 3. COL28A1 appears as a candidate gene in keratoconus genetic etiology 4 and contributes to heart failure pathology, with elevated serum levels correlating with heart failure hospitalization risk, particularly in reduced ejection fraction phenotypes 5. COL28A1 was identified as a prognostic feature gene in glioblastoma 6 and in head and neck squamous cell carcinoma prognosis prediction 7. Additionally, copy number variations in COL28A1 are associated with preterm premature rupture of fetal membranes, suggesting involvement in placental collagen integrity 8.