ST3GAL3 encodes beta-galactoside alpha-2,3-sialyltransferase III, a Golgi enzyme that catalyzes the addition of sialic acid residues to terminal galactose residues on glycoproteins and glycolipids 1. The enzyme creates NeuAc-alpha-2,3-Gal linkages with highest activity toward Gal-beta-1,3-GlcNAc substrates. ST3GAL3 plays critical roles in both normal development and disease pathogenesis. Biallelic loss-of-function variants cause developmental and epileptic encephalopathy 15 (DEE15), characterized by severe intellectual disability, motor impairment, and epilepsy with onset typically in infancy 23. In cancer contexts, ST3GAL3 promotes tumor progression through multiple mechanisms. Elevated ST3GAL3 expression in ovarian cancer creates an immunosuppressive microenvironment by promoting M2-like macrophage polarization and reducing CD8+ T cell infiltration 4. The enzyme also contributes to chemotherapy resistance, as knockdown sensitizes ovarian cancer cells to cisplatin-induced apoptosis through increased caspase activation 5. Recent evidence suggests ST3GAL3 may be involved in ADHD pathogenesis and gastric cancer stem cell maintenance through FOXO-mediated regulation 67. Therapeutically, targeting ST3GAL3-mediated sialylation shows promise for enhancing cancer immunotherapy responses.