Many types of epilepsies are caused by genetic defects in ion channel or neurotransmitter genes, but an alternative epileptogenic mechanism is revealed by dysfunction of the complexes formed by the secreted neuronal glycoprotein LGI1 and its pre- and postsynaptic receptors ADAM23 and ADAM22, respectively.1,2 ADAM22 and ADAM23 are members of the ADAM (A Disintegrin And Metalloproteinase) family of transmembrane proteins implicated in proteolysis and cell adhesion.3 Unlike many ADAM proteins, neuronally expressed ADAM22 and ADAM23 are catalytically inactive and act by binding to other proteins. Here, LGI1 is linked to epilepsy.