B4GALNT3 encodes beta-1,4-N-acetylgalactosaminyltransferase 3, an enzyme that transfers N-acetylgalactosamine (GalNAc) to N-acetylglucosamine residues with β1,4-linkage, forming N,N'-diacetyllactosediamine (LacdiNAc) structures on both N-linked and O-linked glycans 1. The enzyme shows broad specificity, modifying GlcNAc residues on various O-glycan core chains including core 2, core 3, and extended core 1 structures 1. B4GALNT3 plays crucial roles in cancer biology by regulating cancer stemness and invasive properties through modification of EGFR N-glycans, affecting EGFR signaling and degradation in colon cancer 2. In neuroblastoma, B4GALNT3 expression correlates with favorable prognosis and suppresses malignant behavior by modifying β1 integrin glycosylation, leading to decreased focal adhesion kinase and downstream signaling 3. The enzyme is also critical for bone physiology, regulating circulating sclerostin levels through LDN-glycosylation, with B4galnt3-/- mice showing higher sclerostin levels and lower bone mass 4. Genome-wide association studies have identified B4GALNT3 as a significant genetic factor influencing circulating α-Klotho levels, suggesting roles in protein stability and turnover 5. These diverse functions highlight B4GALNT3's importance in cellular signaling, cancer progression, and metabolic regulation.