Ser/Thr-protein kinase WNK4 regulates the activity of the thiazide-sensitive Na-Cl cotransporter SLC12A3 by phosphorylation, which prevents membrane trafficking of SLC12A3. WNK4 also inhibits the renal potassium channel KCNJ1 via a kinase-independent mechanism by which it induces clearance of the protein from the cell surface by clathrin-dependent endocytosis. WNK4 acts as a molecular switch that can vary the balance between NaCl reabsorption and K+ secretion to maintain integrated homeostasis. WNK4 is e, Xenopus/Amphibian,clusively present in intercellular junctions in th edistal convoluted tubule and in both the cytoplasm and intercellular junctions in the cortical collecting duct. Defects in WNK4 are a cause of pseudohypoaldosteronism type II (PHAII).