ST3GAL1 is a Golgi-localized sialyltransferase that catalyzes α2,3-linkage sialylation of core 1 O-glycans and gangliosides, transferring sialic acid from CMP-Neu5Ac onto terminal Galbeta-(1→3)-GalNAc structures. The enzyme regulates CD8+ T cell survival by sialylating glycoproteins including CD43 and CD45, and modulates platelet homeostasis through sialylation of Thomsen-Friedenreich antigen on megakaryocytes 1; aberrant loss of ST3GAL1 function in megakaryocytes exposes cryptic epitopes that trigger type I interferon production by bone marrow immune cells, leading to thrombocytopenia. ST3GAL1 also affects intestinal barrier integrity: reduced ST3GAL1 expression enhances intestinal barrier function and associates with decreased mucosal inflammation in ulcerative colitis, while overexpression impairs barrier function and upregulates pro-inflammatory mediators 2. In cancer, ST3GAL1 overexpression promotes malignancy: in pancreatic adenocarcinoma, ST3GAL1-generated sialic acids engage Siglec receptors on myeloid cells to suppress immune responses 3, while in breast cancer and intrahepatic cholangiocarcinoma, sialylation of neuropilin-1 and activation of NF-κB signaling enhance cell migration and metastatic potential 45. ST3GAL1 has emerged as a candidate therapeutic target for both oncology and immune-mediated disorders. Exome-wide association identified ST3GAL1 variants as contributing to daytime sleepiness in the general population 6.