The ClC 3 chloride channel, also referred to as ClCN 3, belongs to the voltage-gated chloride channels and is ubiquitously expressed throughout the brain and other tissues. Two splice variants of the protein have been described. ClC 3 resides on intracellular trafficking vesicles including synaptic vesicles. It mediates the exchange of chloride ions against protons. In contrast to the translocation of glutamate into synaptic vesicles, the VGAT mediated transport of GABA requires ClC 3. It has been postulated that ClC 3 provides chloride ions as charge balance during the acidification of the vesicle lumen by proton pumping of the V-ATPase.