GAL3ST4 (galactose-3-O-sulfotransferase 4) catalyzes sulfate transfer from PAPS to the C-3 hydroxyl group of terminal galactose residues exclusively in O-linked glycoproteins, particularly core 1 (Gal-beta-1,3-GalNAc-R) structures 1. The enzyme recognizes multiple substrates including core 2 structures and asialofetuin in vitro 1. GAL3ST4 is expressed across diverse tissues, with localization in tumor cells and immune cells 2. In colorectal cancer, GAL3ST4 promotes M2 pro-tumor macrophage polarization, with tumor cell cuproptosis suppressing GAL3ST4 expression to inhibit this phenotypic transition 3. In ovarian cancer, GAL3ST4 preferentially sulfates galactose on the C-3 branch of core structures independent of core type, but unlike other sulfotransferases, shows no differential expression between benign and malignant tissues 4. Notably, GAL3ST4 polymorphisms associate with leprosy susceptibility specifically in females, with high-frequency genotypes showing fivefold elevated expression upon M. leprae antigen stimulation 5. Clinically, GAL3ST4 appears as a prognostic biomarker in multiple malignancies and disease states, including osteosarcoma 2, ruptured abdominal aortic aneurysm 6, and age-related cataracts where it is upregulated 7. Additionally, Gal3st4 upregulation occurs in GPR126-deficient mice modeling idiopathic scoliosis and pectus excavatum 8, suggesting developmental roles.