NFE2L2 and sickle cell disease: Systemic Nrf2 knockout (Nrf2-KO) mice exhibit no abnormalities at birth, during growth, with fertility or throughout their lifespan under normal conditions [32], whereas analyses of Nrf2-KO mice with various disease models have demonstrated that Nrf2 plays protective roles against respiratory disease [33,34,35,36], cardiac disease [37], neurological disease [38,39], diabetes mellitus [40,41,42,43], obesity [44], sickle-cell disease [45], inflammation [46,47], infection [48], liver disease [49,50,51,52] and sensory organ diseases [53,54,55].