LGI1 and epilepsy: Given that the R474Q mutation of LGI1 is actually pathogenic to cause epilepsy in mice (Fig. 3d), the structure of the 2:2 LGI1–ADAM22 complex supports the notion that the pathogenic mechanism of LGI1R474Q is a defect in the assembly of the heterotetrameric ADAM22–LGI1–LGI1–ADAM22/23 complex in synapses.