A new hormone, erythroferrone (ERFE), has been identified as an erythroid regulator of iron metabolism. ERFE is produced by erythroblasts in response to erythropoietin (EPO) and mediates the suppression of hepcidin during stress erythropoiesis. ERFE-deficient mice fail to suppress hepcidin rapidly after hemorrhage and exhibit delayed recovery from blood loss. ERFE expression is significantly increased in murine β-thalassemia intermedia, contributing to hepcidin suppression and systemic iron overload. Hepcidin is a key hormone regulating iron absorption and distribution. It is suppressed during erythropoiesis, allowing increased iron absorption and mobilization from stores. ERFE acts on the liver to suppress hepcidin, facilitating iron delivery to the marrow. ERFE is secreted by erythroblasts and is regulated by the Jak2/Stat5 signaling pathway. ERFE-deficient mice show delayed recovery from hemorrhage, indicating its essential role in hepcidin suppression and iron homeostasis. In β-thalassemia intermedia, ERFE levels are elevated, contributing to hepcidin suppression and iron overload. Ablation of ERFE in these mice reduces hepcidin levels and decreases hepatic iron overload. ERFE is a potent suppressor of hepcidin and acts directly on the liver to repress hepcidin mRNA expression. ERFE is a strong candidate for a pathological hepcidin suppressor in inherited anemias with ineffective erythropoiesis. ERFE's role in hepcidin regulation is independent of the BMP/Smad pathway. ERFE is essential for rapid compensatory response to hemorrhage and is involved in iron metabolism. ERFE's suppression of hepcidin may be beneficial in treating iron-restrictive anemias characterized by increased hepcidin. Further studies are needed to understand ERFE's receptor and downstream effectors, as well as its role in different types of anemia.A new hormone, erythroferrone (ERFE), has been identified as an erythroid regulator of iron metabolism. ERFE is produced by erythroblasts in response to erythropoietin (EPO) and mediates the suppression of hepcidin during stress erythropoiesis. ERFE-deficient mice fail to suppress hepcidin rapidly after hemorrhage and exhibit delayed recovery from blood loss. ERFE expression is significantly increased in murine β-thalassemia intermedia, contributing to hepcidin suppression and systemic iron overload. Hepcidin is a key hormone regulating iron absorption and distribution. It is suppressed during erythropoiesis, allowing increased iron absorption and mobilization from stores. ERFE acts on the liver to suppress hepcidin, facilitating iron delivery to the marrow. ERFE is secreted by erythroblasts and is regulated by the Jak2/Stat5 signaling pathway. ERFE-deficient mice show delayed recovery from hemorrhage, indicating its essential role in hepcidin suppression and iron homeostasis. In β-thalassemia intermedia, ERFE levels are elevated, contributing to hepcidin suppression and iron overload. Ablation of ERFE in these mice reduces hepcidin levels and decreases hepatic iron overload. ERFE is a potent suppressor of hepcidin and acts directly on the liver to repress hepcidin mRNA expression. ERFE is a strong candidate for a pathological hepcidin suppressor in inherited anemias with ineffective erythropoiesis. ERFE's role in hepcidin regulation is independent of the BMP/Smad pathway. ERFE is essential for rapid compensatory response to hemorrhage and is involved in iron metabolism. ERFE's suppression of hepcidin may be beneficial in treating iron-restrictive anemias characterized by increased hepcidin. Further studies are needed to understand ERFE's receptor and downstream effectors, as well as its role in different types of anemia.