NCC-mediated salt reabsorption contributes importantly to blood pressure (BP) regulation: null mutations in the encoding gene, SLC12A3, cause Gitelman’s syndrome, characterized by urinary salt wasting and low BP; “gain-of-function” in NCC, arising from mutations in key regulatory kinases and ubiquitin ligases, causes the hypertensive disorder of pseudohypoaldosteronism type II (25). This evidence concerns the gene SLC12A3 and Gitelman syndrome.