Our subsequent studies using Nedd4-2 C2 KO mice revealed that molecular diversity of the gene encoding Nedd4-2 was also associated with functional diversity, because deletion of merely one of the isoforms encoding Nedd4-2 with C2 domain resulted in uncompensated renal impairment with salt retention and hypertension, as described above. The gene discussed is NEDD4L; the disease is hypertensive disorder.