NFE2L2 and metabolic disease: At the cellular level, Prx4 may promote antioxidant activity via several pathways, such as nuclear factor kB,43 p53,44 thromboxane A2 receptor,45 and NF-E2-related factor 2 (Nrf2).46 Despite equivocal findings of supplementing antioxidant vitamins to prevent cardiovascular and metabolic diseases,1,47 a recent trial48 showed an effective intervention of a specific antioxidant, that is, an Nrf2 antagonist that is related to Prx4 pathway, against decline of renal function in patients with chronic kidney disease and type 2 diabetes.