B4GAT1 (beta-1,4-glucuronyltransferase 1) is a Golgi-localized glycosyltransferase essential for O-mannosyl glycosylation of alpha-dystroglycan (α-DG) 1. The enzyme catalyzes transfer of glucuronic acid onto a xylose acceptor, generating a glucuronyl-β1,4-xylose disaccharide primer 1 that is subsequently elongated by LARGE1 to form phosphorylated O-mannosyl glycans 2. These glycan modifications enable α-DG to bind laminin G-like domain-containing extracellular matrix proteins with high affinity, maintaining tissue integrity and basement membrane organization 1. B4GAT1 localizes to the trans-Golgi network alongside other DG-modifying enzymes 2, functioning at distinct subcellular compartments from its primary localization sites 2. Mutations in B4GAT1 cause muscular dystrophy-dystroglycanopathy type A13, presenting with congenital muscular dystrophy, severe ventriculomegaly, and cerebellar hypoplasia 3. Notably, B4GAT1 downregulation in various human tumors correlates with impaired α-DG glycosylation and disrupted cell-matrix interactions 4. Additionally, B4GAT1 downregulation appears in idiopathic normal pressure hydrocephalus 5, suggesting possible shared molecular mechanisms with congenital hydrocephalus. The gene's role in axon guidance through α-DG O-mannosylation remains important for proper neuromuscular development.