Heparan sulfate glucosamine-6-O-endosulfatase-2 (Sulf-2) is one of the sulfatases that modulates the sulfation status of heparan sulfate proteoglycans (HSPGs), particularly Syndecan-1, in the extracellular hepatic matrix, and it also regulates a number of critical signaling pathways involved in diabetes and lipid trafficking [32]. Here, SULF2 is linked to diabetes mellitus.