GAL3ST3 is a Golgi-resident sulfotransferase that catalyzes sulfation of terminal galactose residues in N-glycans and O-glycans by transferring sulfate from 3'-phosphoadenylyl sulfate (PAPS) to the C-3 hydroxyl position [UniProt]. The enzyme shows strong activity on type 2 chains (Gal-β1,4-GlcNAc) found in N-glycans and core 2-branched O-glycans, with poor activity on type 1 chains and intermediate activity on core 1 structures [PubMed:11323440]. GAL3ST3 participates in synthesis of the 3'-sulfated Lewis X epitope by sulfating N-acetyllactosamine, with subsequent fucosylation by FUT5 generating immunologically relevant structures [PubMed:11356829]. The enzyme is predominantly expressed in brain, kidney, and thyroid tissues [PubMed:11323440]. Disease associations include ovarian cancer, where GAL3ST3-dependent sulfation of N-acetyllactosamine creates epitopes recognized by therapeutic antibodies [PubMed:22194598]. Recent studies identify GAL3ST3 methylation as a biomarker in colorectal cancer with liver metastases, where negative methylation status predicts improved progression-free and overall survival [PubMed:39847896]. GAL3ST3 expression is also upregulated through aryl hydrocarbon receptor signaling to promote mucin sulfation and intestinal barrier integrity [PubMed:41725587], and has been implicated in clozapine-induced myocarditis through altered DNA methylation patterns [PubMed:41170773].