B3GAT3 encodes beta-1,3-glucuronyltransferase 3, a critical enzyme in glycosaminoglycan (GAG) biosynthesis. It catalyzes the transfer of glucuronic acid from UDP-GlcUA to the trisaccharide linkage region (Gal-β1,3-Gal-β1,4-Xyl) on proteoglycans, forming the final tetrasaccharide linker that attaches GAG chains to core proteins 1. This enzyme exhibits strict substrate specificity and also stimulates phosphatase activity during linkage region completion 23. B3GAT3 functions in heparan sulfate, chondroitin sulfate, and dermatan sulfate proteoglycan biosynthesis, with roles in L2/HNK-1 carbohydrate epitope formation on glycoproteins 2. Biallelic B3GAT3 mutations cause linkeropathy, a rare autosomal recessive connective tissue disorder characterized by disproportionate short stature, skeletal dysplasia, facial dysmorphism, and spatulate distal phalanges 14. Variable clinical features include joint hypermobility, contractures, cardiac defects (including aortic root dilation), and bone fragility 15. Genotype-phenotype correlations suggest mutations in the substrate acceptor subdomain cause more severe phenotypes than those in the nucleotide-sugar donor binding domain 1. B3GAT3 is also implicated in hepatocellular carcinoma pathogenesis, with overexpression correlating to poor prognosis, making it a potential cancer therapeutic target 6. Additionally, sulfated GAGs produced via B3GAT3 represent epithelial targets for Candida albicans candidalysin toxin 7.