B3GNT5 (UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 5) is a glycosyltransferase that catalyzes the synthesis of lacto- and neolacto-series glycosphingolipids (GSLs), particularly by converting lactosylceramide and neolactotetraosylceramide into higher-order structures like Lc3Cer and neolactopentaosylceramide 1. The enzyme functions primarily through its glycosyltransferase activity on Golgi membranes during glycosphingolipid biosynthesis 1. B3GNT5 is essential for early embryonic development, as homozygous B3gnt5-null mice exhibit pre-implantation lethality, highlighting its critical role in cell adhesion and differentiation 1. In cancer contexts, B3GNT5 overexpression significantly impacts malignancy across multiple tumor types. Elevated B3GNT5 correlates with poor survival in glioblastoma and thymoma, promotes cancer stem cell properties in basal-like breast cancer, and is associated with chemoresistance and epithelial-mesenchymal transition in various cancers 2 3 4 5. Clinically, B3GNT5-generated GSLs modulate immune responses by impairing HLA-I antigen presentation and CD8+ T cell activation, but paradoxically can function as decoy receptors for pathogenic toxins 6 7. These findings identify B3GNT5 as both a prognostic biomarker and potential therapeutic target for cancer and infectious diseases.