WNK Lysine Deficient Protein Kinase 4 (WNK4)

WNK4 encodes a serine-threonine kinase expressed in distal nephron. Its primary role in renal physiolgy is as a molecular switch between the angiontensin II - aldosterone mediated volume retention and the aldosterone mediated potassium wasting. This is achieved by regulating the sodium-chloride symporter (NCC), that is uniquely expressed in the distal nephron and is sensitive to thiazide type diuretics. WNK4 will inhibit NCC function. It has been proposed that in the event of hyperkalemia and an increased secretion of aldosterone, this inhibition of NCC, will allow an increase in the arrival of sodium to the distal nephron which will allow the exchange of sodium for potassium ions, thereby reducing plasma potassium levels, without increasing sodium chloride retention.