ST6GALNAC4 encodes a sialyltransferase that catalyzes the transfer of sialic acid from CMP-NeuAc to GalNAc residues, forming α-2,6-linkages and producing disialyl-T antigen structures 1. The enzyme shows high efficiency in bacterial expression systems and outperforms some bacterial sialyltransferases in O-glycan modification 2. ST6GALNAC4 plays critical roles in cancer biology, where it functions as part of a glycoimmune checkpoint mechanism. MYC oncogene drives ST6GALNAC4 expression, leading to disialyl-T production that serves as a "don't eat me" signal by engaging Siglec receptors on macrophages, thereby enabling tumor immune evasion 3. In hepatocellular carcinoma (HCC), ST6GALNAC4 promotes malignant progression through abnormal glycosylation of TGFBR2, activating TGF-β signaling and enhancing proliferation, migration, and invasion 4. The enzyme also contributes to immunosuppression through the T antigen-galectin3+ tumor-associated macrophage axis 4. ST6GALNAC4 serves as a prognostic biomarker, with high expression correlating with poor outcomes and reduced immune infiltration in various cancers 35. In thyroid carcinoma, miR-4299 regulates tumor invasiveness by targeting ST6GALNAC4 6. Functionally, ST6GALNAC4 works with ST6GALNAC3 to synthesize disialyl-T structures essential for lymph node vascular integrity 1.