ST3GAL6 is an α-2,3-sialyltransferase that catalyzes the transfer of sialyl residues from CMP-N-acetyl-beta-neuraminate to terminal galactose residues on glycoproteins and glycolipids. This enzyme specifically modifies type II glycan chains (Galbeta1-4GlcNAc) to generate sialyl Lewis X and related structures, which function as selectin ligands critical for neutrophil recruitment during inflammation and lymphocyte trafficking. ST3GAL6 exhibits distinct substrate specificity among α-2,3-sialyltransferases; it preferentially modifies EGFR and other target proteins, with functional consequences distinct from ST3GAL3 and ST3GAL4 1. In multiple myeloma, elevated ST3GAL6 expression correlates with enhanced bone marrow homing, stromal cell adhesion, and inferior overall survival 2. Similarly, in urinary bladder cancer, increased ST3GAL6 associates with advanced tumor stage, grade, and poor prognosis, with the transcription factor GATA3 identified as a direct upstream regulator 3. Conversely, in colorectal cancer, reduced ST3GAL6 expression forms part of a regulatory circuit with long noncoding RNA ST3Gal6-AS1 that suppresses PI3K/Akt signaling and constrains tumor progression 4. Recent evidence suggests ST3GAL6 regulates autophagy in hepatic encephalopathy through the HSPB8-BAG3 complex 5. Human milk oligosaccharide composition is influenced by maternal genetic variation in ST3GAL6 6.