So far only bumetanide, a FDA-approved loop diuretic that acts by antagonizing NKCC1 and NKCC2, has been tested as a potential chloride homeostasis-restoring drug in the context of several diseases, including neonatal seizures, temporal lobe epilepsy, autism and schizophrenia, in preclinical rodent studies and in off-label clinical studies (for a review see140), as well as in adult mouse models of Down syndrome53 and DiGeorge syndrome (22q11.2 microdeletion)141. This evidence concerns the gene SLC12A2 and schizophrenia.