NEDD4-2, the E3-ubiquitin inhibited by SGK1-induced phosphorylation, is involved in ubiquitination and proteasomal degradation, not only of ENaC, but also of NCC and K4.1/Kir5.1 K+ channel, which is related to persistent hypokalemia observed in patients receiving thiazide diuretics, as reported by the absence of this important side effect of thiazide in Nedd4-2-KO animals. This evidence concerns the gene KCNJ16 and Hypokalemia.