There is increasing evidence that ET-1 plays specific roles in podocyte alterations, apoptosis, and loss, nephrin shedding, being implicated in loss of synaptopodin and cytoskeletal rearrangement resulting in foot process effacement, a hallmark of podocytopathies (7, 12, 47, 66) including focal segmental glomerulosclerosis (FSGS) (12, 17). This evidence concerns the gene EDN1 and focal segmental glomerulosclerosis.