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In a series of elegant studies several mechanisms that direct Nrf2 into the nucleus have been described (reviewed in [81]): (i) oxidation of specific cysteine residues of Keap1 resulting in its inability to bind Nrf2, (ii) interaction of nucleophilic molecules with cysteine residue(s) of Keap1 leading to the formation of adducts that prevent binding to Nrf2, (iii) phosphorylation of Nrf2 by different protein kinases, and (iv) ubiquitination of Keap1 followed by proteasomal hydrolysis (Figure 5)