Under hypoxia, YAP binds to nuclear HIF-1α and sustains its stability, thereby promoting the expression of pyruvate kinase isozymes M2 (PKM2), a key enzyme of glycolysis, in, for example, hepatocellular carcinoma cells (HCCs) (Zhang X. et al., 2018), whereas in the cytoplasm, YAP enhances HIF-1α stability by inhibiting VHL-dependent degradation of hydroxylated HIF-1α (Ma et al., 2015; Zhao et al., 2020) (Figure 1A). The gene discussed is YAP1; the disease is hepatocellular carcinoma.