After erythropoietic stimulation, differentiating erythroblasts in the bone marrow and spleen rapidly increase ERFE production in an EPO- and STAT5- dependent manner. ERFE is secreted into the circulation and acts directly on the liver to repress hepcidin production. ERFE-mediated hepcidin suppression in turn increases iron availability for new red blood cell synthesis.Reprinted by permission from Macmillan Publishers Ltd: Nature Genetics. 2014;46(7):678-684, copyright 2014.