EPAS1 and hereditary disease: We hypothesized that changes in either systemic or intestinal copper status regulate HIF-2α and as consequence iron absorption genes since: (i) we and others have shown that Cybrd1, Slc11a2 and Slc40a1 are bona fide Hif-2α targets [6], [7]; (ii) in vitro evidence suggests that changes in cellular copper levels regulate HIF-1α [20] and (iii) anemia associated with genetic disorders of copper metabolism could lead to increases in tissue hypoxia and stabilize HIF-2α [21]–[25].