In the mature brain, the neurotransmitter GABA can cause a postsynaptic hyperpolarization via activation of chloride permeant GABAA receptor channels. This hyperpolarizing response critically depends on chloride extrusion via the KCl-cotransporter KCC2 . Its knockdown in mice impairs synaptic inhibition by changing the electrochemical potential for chloride and thus increases neuronal excitability ,. Two independent groups provide first evidence now, published in EMBO reports, that rare variants of KCC2 confer an increased risk of epilepsy in men ,.