The KEAP1:NFE2L2 (Keap1-Nrf2, Kelch-like ECH-associated protein 1-nuclear factor (erythroid-derived 2)-like 2) regulatory pathway plays a central role in protecting cells against oxidative and xenobiotic stresses. The NFE2L2 transcription factor activates the transcription of several cytoprotective genes that have been implicated in protection from cancer and neurodegenerative diseases (Deshmukh et al, 2017).

KEAP1 forms part of an E3 ubiquitin ligase, which tightly regulates the activity of the transcription factor NFE2L2 by targeting it for ubiquitination and proteasome-dependent degradation. In response to stress, an intricate molecular mechanism facilitated by sensor cysteines within KEAP1 allows NFE2L2 to escape ubiquitination, accumulate within the cell, and translocate to the nucleus, where it can promote its antioxidant transcription program (Baird and Yamamoto, 2017).