In recent years, a large body of constantly increasing experimentalevidence has indicated modulation of intracellular chloride concentration[Cl–]i as a valuable therapeutic strategyfor a number of neurological conditions, including Down syndrome (DS).1−3 [Cl–]i is mainly regulated in neuronsby the sodium (Na+)–potassium (K+)–chloride(Cl–) importer NKCC1 and the K+–Cl– exporter KCC2. The gene discussed is SLC12A2; the disease is Down syndrome.