WNK1 controls sodium and chloride ion transport by inhibiting the activity of WNK4, potentially by either phosphorylating the kinase or via an interaction between WNK4 and the autoinhibitory domain of WNK1. WNK4 regulates the activity of the thiazide sensitive Na Cl cotransporter, SLC12A3, by phosphorylation. WNK1 may also play a role in actin cytoskeletal reorganization.WNK1 has 4 isoforms produced by alternative splicing. WNK1 is widely expressed, with highest levels observed in the testis, heart, kidney and skeletal muscle.Defects in WNK1 are a cause of pseudohypoaldosteronism type II (PHAII), an autosomal dominant disease characterized by severe hypertension, hyperkalemia, and sensitivity to thiazide diuretics which may result from a chloride shunt in the renal distal nephron.