Recently, we generated WNK4D561A/+ knock-in mice, an ideal mouse model of PHAII, and found that the pathogenesis of PHAII is the constitutive activation of the WNK-OSR1/SPAK kinases-NaCl cotransporter (NCC) cascade, resulting in gain of function of NCC [3]. This evidence concerns the gene OSR1 and pseudohypoaldosteronism type 2.