B4GALNT4 encodes beta-1,4-N-acetyl-galactosaminyltransferase 4, a glycosyltransferase that transfers N-acetylgalactosamine (GalNAc) from UDP-GalNAc to N-acetylglucosamine with beta-1,4 linkage, forming GalNAcβ1-4GlcNAc (LacdiNAc) structures in N-linked and O-linked glycans 1. The enzyme contains a unique noncatalytic PA14 domain essential for catalytic activity toward various glycan substrates 1. Unlike the dominant subterminal structure LacNAc, LacdiNAc formation by B4GALNT4 negatively impacts downstream glycan modifications including sialylation and fucosylation, and is nearly completely inhibited by prior bisecting GlcNAc formation 1. B4GALNT4 has significant disease relevance. Expression is elevated in multiple cancers including prostate and esophageal squamous cell carcinoma 2, 3. In esophageal cancer, B4GALNT4 knockdown suppressed proliferation, invasion, migration, and adhesion; high expression independently predicted poor disease-free and disease-specific survival 3. In prostate cancer, B4GALNT4 is a key component of a cuproptosis-related prognostic signature associated with immunosuppressive microenvironments and poor outcomes 2. Elevated B4GALNT4 and altered PSA glycosylation distinguish prostate cancer from benign hyperplasia with >95% discrimination probability 4. Additionally, B4GALNT4 methylation associates with offspring adiposity changes 5. Clinically, B4GALNT4 knockout in engineered HEK293 cell lines improves therapeutic protein pharmacokinetics by reducing rapid clearance 6.