ST3GAL1 is a sialyltransferase that catalyzes the transfer of sialic acid onto acceptor galactose residues through α2,3 linkages, adding sialic acid to core 1 O-glycans and gangliosides 1. The enzyme modifies glycoproteins and glycolipids in the trans-Golgi network, with major substrates including T cell glycoproteins (CD43, CD45) and immune cell markers 2. ST3GAL1 plays critical roles in immune regulation and cancer biology. In T cell homeostasis, ST3GAL1-mediated sialylation prevents premature apoptosis of thymic CD8+ T cells and controls memory T cell survival in secondary lymphoid organs 2. However, in the context of CAR T cell therapy, ST3GAL1 acts as a negative regulator—its glycosylation of CD18 induces nonspecific tissue sequestration through altered LFA-1 recycling, reducing tumor-specific homing 3. In cancer progression, elevated ST3GAL1 expression contributes to malignant phenotypes across multiple cancer types. ST3GAL1-mediated sialylation of neuropilin-1 increases EGFR binding affinity, enhancing breast cancer cell migration and metastasis 4. In pancreatic cancer, ST3GAL1-generated sialic acids promote immunosuppression by engaging Siglec-7 and Siglec-9 receptors on tumor-associated macrophages 5. In intrahepatic cholangiocarcinoma, ST3GAL1 overexpression activates NF-κB signaling to promote proliferation and invasion 6. Clinically, ST3GAL1 dysfunction associates with disease pathogenesis. Genetic variants in ST3GAL1 correlate with daytime sleepiness 7, and altered ST3GAL1 expression in intestinal epithelial cells impairs barrier function in ulcerative colitis through disrupted MUC2 and TFF3 expression 8. Additionally, ST3GAL1 deficiency in megakaryocytes causes thrombocytopenia through immune recognition of exposed TF antigens 9.