COLGALT2 encodes collagen beta(1-O)galactosyltransferase 2, a key enzyme that initiates collagen glycosylation by transferring β-galactose to hydroxylysine residues 1. The enzyme operates in the endoplasmic reticulum alongside COLGALT1 to catalyze the first step of collagen post-translational modification, which is essential for proper collagen fibril organization and extracellular matrix function 12. COLGALT2 glycosylates various collagen types, with basement membrane collagen type IV being more extensively modified than fibrillar collagens 1. The enzyme's activity influences collagen secretion, fibril alignment, and mechanical properties 2. Disease-wise, COLGALT2 variants have been associated with osteoarthritis susceptibility through epigenetic regulation mechanisms 34, and mutations may contribute to connective tissue disorders like rectal prolapse 5. Clinically, COLGALT2 serves as a target for multiple independent osteoarthritis risk loci that modulate its expression through DNA methylation changes in tissue-specific enhancers 64. The gene also shows prognostic significance in various cancers, including nephroblastoma and colorectal cancer 78.