FUT3 is a fucosyltransferase that catalyzes the transfer of L-fucose to N-acetylglucosamine and glucose residues on glycans, synthesizing Lewis blood group antigens (Le(a), Le(b), Le(x), Le(y)) and sialyl Lewis structures 123. The enzyme preferentially acts on type 1 chain acceptors and is essential for determining Lewis blood group phenotypes, with Lewis-positive individuals expressing active enzyme while Lewis-negative individuals lack functional activity 3. Beyond its role in blood group antigenicity, FUT3-synthesized fucosylated glycans regulate cell-cell adhesion through E-selectin binding and modulate cell migration and proliferation 45. FUT3 polymorphisms associate with susceptibility to infectious diseases: specific alleles increase H. pylori infection risk in Chinese populations 6, and variants influence Crohn's disease susceptibility and lesion location 7. In cancer contexts, FUT3 promotes gastric cancer cell migration by synthesizing Le(a) antigens on integrin α6 and GLG1, affecting adhesion and intracellular vesicle distribution 8. High FUT3 expression correlates with pancreatic cancer chemoresistance through B3GNT3-mediated NF-κB signaling and autophagy activation 9. Conversely, FUT3 absence associates with reduced breast cancer development, suggesting context-dependent roles in malignancy 10. FUT3 expression responds to microenvironmental stress, with differential regulation under hypoxia and serum deprivation in breast cancer cells 11. Human milk oligosaccharide composition is influenced by maternal FUT3 genetic variants and lactation stage 12.