ST6GAL1 is a sialyltransferase that catalyzes α2,6-sialylation of N-glycosylated proteins in the Golgi apparatus 1. The enzyme transfers sialic acid to galactose-containing acceptors on glycoproteins, generating neuraminidase-sensitive cell-surface differentiation antigens and conferring anti-inflammatory properties to immunoglobulin Fc regions [UniProt annotation]. ST6GAL1 has context-dependent roles in cancer biology. In prostate cancer, ST6GAL1 upregulation promotes bone metastasis by modifying the pre-metastatic niche and promoting immunosuppressive macrophages 1. Similarly, in colorectal cancer, ST6GAL1-mediated sialylation stabilizes PD-L1, driving immunosuppression and poor prognosis, while ST6GAL1 inhibition enhances anti-PD-L1 therapy efficacy 2. In pancreatic cancer, ST6GAL1 promotes acinar-to-ductal metaplasia through EGFR activation 3. However, in breast cancer, hyposialylation—loss of ST6GAL1 activity—promotes chemotherapy evasion and metastatic seeding of quiescent tumor cell clusters 4. In hepatocellular carcinoma, ST6GAL1 unexpectedly inhibits metastasis by sialylating MCAM, reducing its surface expression 5. In glioma, lower ST6GAL1 expression correlates with poor prognosis 6. These findings reveal ST6GAL1's role in immunomodulation and tumor progression varies by cancer type, representing both therapeutic target and biomarker potential.