The chloride channel CIC-1 was originally thought to function largely in skeletal muscle, but findings reported in Neurology suggest an additional role in the modulation of neuronal excitability. Jeffrey Noebels and colleagues found widespread expression of the CIC-1-encoding gene CLCN1 in mouse and human brain tissue, and also discovered CLCN1 missense variants in a high proportion of patients with sporadic epilepsy.