We designed a cell‐permeable peptide able to interfere with ERK1, ERK2, and KPNA2 interactions, thus selectively potentiating nuclear ERK activation, attenuating neuronal cell loss in models of neurodegeneration, improving cognition in healthy rodents, and rescuing cognitive deficits in Alzheimer's (AD) and Huntington's (HD) disease mouse models. This evidence concerns the gene KPNA2 and Alzheimer disease.