Expression of heparanase is restricted primarily to the placenta, keratinocytes, platelets, and activated cells of the immune system, with little or no expression in connective tissue cells and most normal epithelia.9,10 Up-regulated expression of heparanase was noted in essentially all human tumors examined, as well as in inflammation, wound healing, and diabetic nephropathy.9–11 During embryogenesis, the enzyme is preferentially expressed in cells of the developing vascular and nervous systems.16 Here, HPSE is linked to diabetic kidney disease.