Heparan sulfate proteoglycans (HSPGs) are glycoconjugates that consist of a core protein linked to one or more linear heparan sulfate (HS) chains. The chains are composed of alternating N-acetyl-D-glucosamine and glucuronic acid or iduronic acid that can be variably N- and O-sulfated. HS synthesis occurs in the Golgi apparatus. It starts with the formation of a tetrasaccharide linker on the core protein followed by the alternating addition of glucuronic acid and N-acetylglucosamine residues. Glucuronic acid can undergo epimerization into iduronic acid, which together with N-acetylglucosamine residues, can be sulfated. HSPGs are then transported to the plasma membrane where they can be processed further by endosulfatases such as Sulf1 that remove sulfate groups from specific sites. (Adapted from FBrf0232460 and FBrf0228609.)