Schematic diagram depicting phenotypic findings in Erfe-transgenic mice. Erythroid cells overexpress and secrete ERFE, which circulates to the liver, where it acts as a BMP ligand trap to inhibit SMAD signaling and hepcidin transcription. Hepcidin suppression stabilizes ferroportin (FPN) expression on duodenal enterocytes, iron-recycling macrophages, and iron-storage hepatocytes to increase iron release into circulation to support erythropoiesis. Excess iron deposits in the liver and other tissues. At the highest levels, excess ERFE also acts on other organ systems, leading to perinatal lethality, impaired growth, reduced kidney size and function, decreased gonadal fat depots, and neurobehavioral abnormalities.