Is N-sulfation just a gateway modification during heparan sulfate biosynthesis?

► Heparan sulfate (HS) biosynthesis is a complex multi-step process. ► N-Deacetylase-N-sulfotransferase (NDST) converts GlcNHAc to GlcNHSO3- residues. ► NDST is considered as a gateway enzyme because it carries out the first modification. ► We show that O-sulfation does not inhibit NDST and NDST can also catalyze maturation. ► We redefine the dynamic role of NDST in the GAGOSOME.