The concentration of glutamate within a glutamatergic synapse is tightly regulated by the excitatory amino acid transporters (EAATs).In addition to their primary role of clearing extracellular glutamate, the EAATs also possess a thermodynamically uncoupled chloride (Cl-) conductance.This Cl-conductance has been proposed to play roles in regulating ionic homeostasis and glutamate release in the retina and is present in all members of the glutamate transporter family.Several crystal structures of an archaeal homologue of the EAATs, GltPh, at different stages of the transport cycle have been solved.In a recent structure, a small cavity located at the interface of the transport and trimerisation domains has been identified and is lined by polarizable residues, several of which have been implicated in Cl-permeation.We hypothesize that throughout the transport cycle this cavity opens up to form the Cl-channel.