Under physiological conditions, Keap1 keeps the Nrf2 transcription factor in the cytoplasm, allowing it to be ubiquitinated and degraded by proteasomes; but when cells are exposed to neurodegenerative disease-mediated oxidative stress, a signal involving phosphorylation and/or redox modification in Keap1 blocks the enzymatic activity of the Keap1-Cul3-Rbx1 E3 ubiquitin ligase complex, leading to decrease in Nrf2 ubiquitination and degradation. Here, NFE2L2 is linked to neurodegenerative disease.