PTPN5 and Alzheimer disease: Given that STEP61 level is elevated in human AD which displays epileptic seizures as a comorbid condition [10–13], we hypothesize that hippocampal neuronal hyperexcitability induced by seizures will increase STEP61 level, leading to compensatory downregulation of synaptic strength by dephosphorylating GluN2B, GluA2, and ERK1/2, key proteins critical for synaptic plasticity.