Although IDH1/IDH2 mutations are relatively rare in bladder cancer (∼2%), their dysfunction has notable ‘metabolite–epigenetic’ cascade effects: mutant IDH1 (e.g., R132H) loses its normal catalytic activity and instead produces high levels of 2-hydroxyglutarate (2-HG) in an NADPH-dependent manner. The gene discussed is IDH1; the disease is urinary bladder cancer.