GAL3ST3 (galactose-3-O-sulfotransferase 3) catalyzes the transfer of sulfate groups from 3'-phosphoadenylyl sulfate (PAPS) to the C-3 hydroxyl group of terminal non-reducing β-1,4-linked galactose residues in both N-glycans and O-glycans 123. The enzyme shows high activity on type 2 chains (Gal-β-1,4-GlcNAc-R) and core 2-branched O-glycans, while demonstrating poor activity on type 1 chains and intermediate activity on core 1 structures 123. GAL3ST3 participates in glycoconjugate sulfation, particularly in forming the 3'-sulfated Lewis X epitope by sulfating N-acetyllactosamine at the 3' position 2. The enzyme plays critical roles in immune modulation and disease processes. It contributes to Siglec ligand formation through carbohydrate sulfation, affecting immune recognition mechanisms 4. GAL3ST3 is also involved in cancer biology, as its methylation status serves as a biomarker for colorectal liver metastases prognosis 5 and is associated with cognitive function changes related to arsenic exposure 6. Additionally, GAL3ST3 supports intestinal barrier function through mucin sulfation via AHR-mediated transcriptional regulation 7. The enzyme's tissue-specific expression pattern enables recognition by specialized antibodies targeting 3-O-sulfated galactose epitopes 8.