EXTL2-related Glycosaminoglycan Biosynthesis and Disease

Mutant alleles of EXT1 or EXT2, two members of the exostosin (EXT) gene family, are causative agents of hereditary multiple exostoses, and their gene products function together as a polymerase in the biosynthesis of heparan sulfate. EXTL2 is one of the three EXT-like genes homologous to tumor suppressor EXT gene family members and encodes an N-acetylhexosaminyltransferase. However, the role of EXTL2 in the biosynthesis of glycosaminoglycan (GAG) and the biological significance of EXTL2 were previously unclear. Our studies have revealed that EXTL2 controls GAG biosynthesis, and abnormal biosynthesis of GAGs due to the loss of EXTL2 affects pathological processes. In this minireview, we focus on the functional importance of EXTL2 in GAG biosynthesis and how decreased EXTL2 expression is involved in the progression of various diseases.