Although the matrix metalloprotease (MMP) enzyme family can cleave HS proteoglycan core proteins found in the eGlx such as Syndecan-4 [24, 25], heparanase-1 is the only known mammalian endoglycosidase with the capability to directly cleave HS, and is systemically upregulated in diabetes. The gene discussed is HPSE; the disease is diabetes mellitus.