The central role of the kinase WNK4 in modulation of NCC activity was discovered when mutations on Wnk genes were responsible for around 20% of the clinical manifestations of pseudohypoaldosteronism type II (PHAII), characterized by hyperkalemia and hypertension, due to hyperactivity of NCC. This evidence concerns the gene SLC12A3 and pseudohypoaldosteronism type 2.