ST6GALNAC1 is a sialyltransferase specifically expressed in goblet cells that catalyzes α-2,6 sialylation of N-acetylgalactosamine (GalNAc) residues on glycoproteins, forming the sialyl-Tn (sTn) antigen 1. This sialylation is essential for intestinal mucus integrity and protects against bacterial proteolytic degradation 1. Beyond the intestine, ST6GALNAC1-mediated sTn on CD44 facilitates embryo implantation through interaction with trophoblastic Siglec receptors 2, and conjunctival goblet cell sialylation protects against allergic inflammation 3. In disease contexts, decreased ST6GALNAC1 activity causes defective mucus proteins and congenital inflammatory bowel disease (IBD), with patient mutations producing compromised mucus barriers and dysbiosis 1. Conversely, ST6GALNAC1 upregulation is observed in cancer progression. ST6GALNAC1 expression is elevated in ulcerative colitis and colitis-associated colon cancer through macrophage-derived IL-13/STAT6 signaling 4. In breast cancer, elevated ST6GALNAC1 promotes cell invasion and migration via epithelial-mesenchymal transition (EMT) 5. However, in colorectal cancer, ST6GALNAC1 expression is paradoxically downregulated, correlating with poor survival 6. ST6GALNAC1-regulated sTn is recognized as an onco-fetal antigen linked to tumor progression across multiple cancer types 7. Host genetic variation in ST6GALNAC1 also influences microbiome composition, with associations to Paraprevotella linked to immune function 8.