In the present study, we have shown that administration of the interfering GluR2NT1-3–2 peptide to interrupt the GluR2/GAPDH interaction significantly mitigates neuronal cell death in a cell model of ischemia, revealing a previously unappreciated signaling pathway underlying AMPAR-mediated excitotoxicity and it may provide a new avenue for the development of a complementary therapeutics in the treatment of neuropathological disorders, such as stroke and epilepsy. This evidence concerns the gene GAPDH and epilepsy.