Similarly to HIF-1α, HIF-2α is activated in hypoxic conditions through a common signaling pathway (Hu et al., 2022), causing a more relevant response to hypoxia due to its higher affinity for the promoters of genes involved in the hypoxia response (Hu et al., 2022), which results also in an enhanced inducing activity of HIF-2α in some cancers (Wu et al., 2019). The gene discussed is EPAS1; the disease is cancer.