A similar dysregulation of the IRP-1/HIF-2α pathway, which links erythropoiesis and iron availability, leads to unabated expression of the HIF-2α-target gene erythropoietin (EPO) and polycythemia in rare patients with mutations in IRP1 [19] and IRP1-knockout mice [20]. Here, ACO1 is linked to polycythemia.