Through the analysis of WNK4D561A/+ PHAII model mice crossed with Osr1 and Spak knock-in mice, we showed that the pathogenesis of hypokalaemia is also the result of NCC activation by WNK–OSR1/SPAK signalling, but is not caused by a direct effect of mutant WNK4 on ROMK. The gene discussed is SLC12A3; the disease is Hypokalemia.