The notion that the NCC is important for regulating K+ excretion is also supported by the facts that two genetic diseases, Gitelman syndrome (caused by the loss-of-function of NCC) and pseudohypoaldosteronism type II (caused by the gain-of-function of NCC) show hypokalemia and hyperkalemia, respectively [11,12]. The gene discussed is SLC12A3; the disease is pseudohypoaldosteronism type 2.