Changes in Cl− regulation are likely to have an important role in the molecular etiology of a number of psychiatric and neurological diseases—since some of the deleterious effects on neuronal development and function have been connected with elevated [Cl−]i and/or cell volume and increased strength of GABA signaling, a number of recent efforts have focused on inhibition of NKCC1, inhibition of WNK-SPAK/OSR1, or on finding agonists to increase KCC2 transport activity and membrane trafficking19,26. This evidence concerns the gene SLC12A5 and nervous system disorder.