In addition, ∆Np63α-arbitrated lymphoid-specific helicase (Lsh) upregulation77 can epigenetically suppress fumarate hydratase (FH), a Krebs cycle enzyme.81 This leads to the accumulation of fumarate, considered an oncometabolite, which then inhibits the inhibitors of hypoxia-inducible factor (HIF), the prolyl hydroxylases (PHDs).82 Consequently, amplified HIF can promote malignancy through the Warburg effect by providing cancer cells with building blocks (Fig. 3b).83 The gene discussed is HELLS; the disease is cancer.