GAL3ST2 (galactose-3-O-sulfotransferase 2) is a key enzyme that catalyzes the sulfation of galactose residues in glycans by transferring sulfate groups from PAPS to the C-3 hydroxyl group of terminal β-galactosyl residues 1. The enzyme acts on both type 1 and type 2 carbohydrate chains and participates in the modification of various glycan structures including lactose, lacto-N-tetraose, and mucin core-2 structures 1. Mechanistically, GAL3ST2 preferentially sulfates galactose on the C-6 branch of core 2 O-glycan structures and modulates cellular glycosylation patterns 1. This sulfation activity has broad biological significance, as GAL3ST2-mediated glycan modifications can restrict sialic acid-dependent viral infections by reducing viral attachment during entry 2. Disease relevance is evident in multiple cancers: GAL3ST2 expression decreases in ovarian cancer with lowest levels in poorly differentiated malignant tissue 1, while the D2HGDH-GAL3ST2 fusion RNA is enriched in prostate cancer and associated with late-stage disease 3. Clinically, low GAL3ST2 protein levels correlate with poor patient outcomes in colorectal cancer 4, and GAL3ST2 polymorphisms can improve diagnostic accuracy of CA19-9 tumor marker assays for pancreatic cancer detection 5.