LGI1 and epilepsy: Consistently, a recent study showed that loss of the ADAM22 PDZ ligand (i.e. C-terminal five amino acids) causes lethal epilepsy around 2–8 months of age in mice and that the LGI1–ADAM22–PSD-95 interaction is a key player in the trans-synaptic nanoarchitecture for precise synaptic transmission.10 Pathogenic genetic variants in DLG4, encoding PSD-95, have been recently identified in subjects with intellectual disability,35,36 highlighting the importance of PSD-95 in human brain development.