Proteoglycan N-acetylglucosaminyltransferases catalyze the transfer of N-acetylglucosamine (GlcNAc) to proteoglycans, such as heparan sulfate proteoglycans (HSPGs). HSPGs consist of a protein core to which heparan sulfate (HS) glycosaminoglycan (GAG) chains are attached. The biosynthesis of HS GAG chains is initiated by the formation of a GAG-protein linkage region consisting of a tetrasaccharide attached to specific serine residues in a proteoglycan core protein. Both the attachment of the first GlcNAc to the GAG-protein linkage region and the subsequent polymer formation are catalyzed by members of the hereditary multiple exostoses (EXT) gene family of tumor suppressors, or their orthologs. HSPGs are implicated in regulating the signalling activities of secreted morphogen molecules including Wingless (Wg), Hedgehog (Hh) and Decapentaplegic (Dpp). (Adapted from FBrf0174560.)