NFE2L2 and cancer: For instance, KEAP1 encodes the adapter protein of an E3 ligase complex which can ubiquitinate NRF2, and previous studies have proven that mutations in KEAP1 and NFE2L2 may lead to NRF2 activation which may further contribute to spontaneous cancer development (Leinonen et al. 2014; Taguchi et al. 2010).