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]. Here, SLC12A3 is linked to Gitelman syndrome.