Therefore, blocking WNK-SPAK/OSR1 may provide a potent means of synchronously inhibiting of NKCC1-mediated Cl- influx and enhancing KCC-mediated Cl- extrusion for multiple syndromes exhibiting depolarized GABA responses and altered Cl- homeostasis, cerebral edema, or hydrocephalus. The gene discussed is SLC12A2; the disease is edema.