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Molecular responses mediated by sensor proteins are important for biological defense against electrophilic stresses, such as xenobiotic electrophile exposure. NF-E2-related factor 2 (Nrf2) has an essential function as a master regulator of such cytoprotective molecular responses along with sensor protein Kelch-like ECH-associated protein 1. This review focuses on Nrf2 activation and its involvement with the protective defense systems under electrophilic stresses integrated with our recent findings that reactive sulfur species (RSS) mediate detoxification of electrophiles. The Nrf2 pathway does not function redundantly with the RSS-generating cystathionine γ-lyase pathway, and vice versa. [ABSTRACT FROM AUTHOR]