Although the underlying mechanism of tau-mediated neurodegeneration in epilepsy is not completely understood, there is evidence that tau contributes to epileptogenesis, mainly by reducing PP2A activity, increasing the activity of GSK3β and CDK5, activating the PI3K/AKT pathways, promoting the NMDAR subtype 2B (NR2B) receptor-mediated glutamate release, and stimulating NMDAR [123]. The gene discussed is MAPT; the disease is epilepsy.