Importantly, a cell membrane‐permeable peptide that preserve Nrf2 SUMOylation by blocking the direct interaction of SENP6 and Nrf2 shows comparable neuroprotective effects, as evidenced by reduced oxidative stress and brain neuronal loss, mitigated neurological deficit scores, and improved long‐term neurological function in an animal model of stroke, which laying the groundwork for the development of potential therapeutic strategies for ischemic stroke. The gene discussed is NFE2L2; the disease is stroke disorder.