ST3GAL4 is a beta-galactoside alpha-2,3-sialyltransferase that catalyzes terminal sialylation of glycoproteins and glycolipids by transferring sialic acid onto acceptor glycoconjugates 12. The enzyme plays critical roles in hemostasis by sialylating von Willebrand factor, preventing its clearance by asialoglycoprotein receptors 3. ST3GAL4 synthesizes sialyl Lewis X epitopes recognized by selectins, facilitating leukocyte adhesion and extravasation during immune responses 4. In ganglioside biosynthesis, ST3GAL4 produces LM1, a major component of peripheral nerve myelin 2. ST3GAL4 expression is significantly elevated in multiple malignancies, where it generates ligands for Siglec receptors on immune cells, thereby promoting immune evasion. In pancreatic cancer, ST3GAL4-mediated sialylation on cancer-associated fibroblasts drives macrophage differentiation toward immunosuppressive phenotypes via Siglec-7 and Siglec-9 interactions 56. Similarly, in acute myeloid leukemia, ST3GAL4 synthesizes N-linked sialoglycans recognized by Siglec-9, reducing phagocytosis by macrophages 7. In osteosarcoma, ST3GAL4 knockdown inhibits tumor cell proliferation, migration, invasion, glycolysis, and M2 macrophage polarization 8. ST3GAL4 transcriptional regulation involves multiple promoters responsive to immune signals including NFAT binding sites 9. Genetic variants in ST3GAL4 associate with plasma VWF levels and Factor VIII activity, indicating clinical relevance for thrombotic disorders 3.