Similar to the IDH1 R132 mutation, the cancer-associated IDH2 R172 mutation was demonstrated to be deficient in isocitrate-dependent NADPH production (Yan et al., 2009; Ward et al., 2010), while acquiring a gain of function for alpha-ketoglutarate-dependent NADPH consumption that resulted in the production of 2HG (Ward et al., 2010). The gene discussed is IDH1; the disease is cancer.