HPSE and Renal insufficiency: Firstly, it was observed that endothelin-1 activates podocytes to release heparanase, thus causing damage to the glycocalyx, proteinuria, and renal failure [99]; secondly, it was observed that heparanase overexpression increases ET-1 levels after I/R renal injury [77], and heparanase inhibition reduces ET-1 expression [77,88] and its associated renal fibrosis [88].