The physiological role of these proteins was clarified by the generation of the Clcnk1−/− mouse (ClC-K1 is the rodent homolog of ClC-Ka) with pronounced diabetes insipidus and the linkage of CLCNKB to Bartter syndrome, a human condition characterized by impaired renal urine concentration resulting in hypotension with elevated renin and aldosterone levels (Simon et al., 1997; Matsumura et al., 1999). The gene discussed is CLCNKB; the disease is Bartter syndrome.