As 10–25% of patients with 22q11DS develop epilepsy [219] and Cldn5 KD mice develop epilepsy [180], CLDN-5 decline might be an initial trigger for seizures and epilepsy due to the extravasation of blood-borne proteins or induction of neuroinflammation [220], but it mainly contributes to increasing the severity and vulnerability of recurrent epilepsies. The gene discussed is CLDN5; the disease is epilepsy.