COLGALT1 encodes collagen beta(1-O)galactosyltransferase 1, a key enzyme in collagen post-translational modification. The protein transfers beta-galactose residues to hydroxylysine residues in collagen chains within the endoplasmic reticulum 1, facilitating collagen triple helix formation 2 and type IV collagen biosynthesis 3. Structurally, COLGALT1 forms an elongated head-to-head homodimer with two domains (GT1 and GT2), with the catalytic site located in the GT2 domain featuring a distinctive Glu-Asp-Asp motif coordinating Mn2+ cofactors 4. The enzyme functions as part of the KOGG complex—a fiber-like oligomeric assembly with lysyl hydroxylase PLOD3—orchestrating sequential hydroxylation and dual glycosylation of procollagen 5. Clinically, biallelic COLGALT1 mutations cause cerebral small vessel disease and porencephaly through impaired type IV collagen secretion, mirroring COL4A1/COL4A2-related pathologies 13. Emerging evidence suggests COLGALT1 serves as a prognostic biomarker in glioblastoma and kidney renal clear cell carcinoma, where elevated expression correlates with poor prognosis and altered immune microenvironment composition 67.