HAMP and Tangier disease: ERFE-knockout mice were unable to inhibit hepcidin production rapidly after hemorrhage and recovered slowly after blood loss.110 In contrast, ERFE overexpression resulted in iron overload and developmental abnormalities in mice.111 Hepcidin expression is also upregulated during inflammation; for instance, interleukin-6 (IL-6) directly regulates hepcidin expression by activating signal converter and activator of transcription 3,112 and the bone morphogenetic protein signaling pathway is required for IL-6-induced hepcidin expression.113