GALNT18 (polypeptide N-acetylgalactosaminyltransferase 18) catalyzes the initial step of O-linked oligosaccharide biosynthesis by transferring N-acetyl-D-galactosamine (GalNAc) from UDP-GalNAc to serine or threonine residues on protein substrates, functioning in the Golgi apparatus. The enzyme is upregulated during mucin-type Golgi stress, where it coordinates with other GALNT family members to augment glycosylation capacity 1. GALNT18-mediated O-glycosylation has clinical significance across multiple disease contexts. In rheumatoid arthritis patients treated with tocilizumab, the GALNT18 rs4910008 C-allele polymorphism independently predicts superior treatment response, remission, and disease activity improvement at both 6 and 18 months 23. In nonalcoholic steatohepatitis-associated hepatocellular carcinoma, GALNT18 directly interacts with amyloid precursor protein (APP) and promotes its O-glycosylation, which activates oncogenic EGR1/TGF-β1/Smad signaling, driving hepatocellular carcinoma progression 4. Additionally, the GALNT18 rs9943588 variant associates with increased early menopause risk in Iranian women and poor ovarian reserve 5. GALNT18 variants also associate with chr11 kidney disease susceptibility in canine models 6 and milk composition traits in dairy cattle 7, suggesting broader roles in metabolic regulation.