When ClC-6 was converted from a 2Cl−/H+ exchanger into a pure Cl− conductance by the uncoupling E200A mutation, which by itself leads to moderately enlarged vesicles (4) and is associated with a distinct neurological disorder (35, 36), additional insertion of the T520A mutation (E200A/T520A) no longer enlarged vacuoles to the same degree (fig. Here, CLCN6 is linked to nervous system disorder.