ERFE (erythroferrone) is an iron-regulatory hormone that serves as a critical mediator in systemic iron homeostasis and erythropoiesis. The protein functions primarily as an erythroid regulator produced by erythroblasts following blood loss, where it suppresses hepcidin (HAMP) expression in the liver, thereby promoting increased iron absorption and mobilization from stores 1. This hepcidin inhibition is particularly important in congenital dyserythropoietic anemias (CDAs), where erythroferrone specifically mediates hepatic iron overload 1. Beyond iron metabolism, ERFE acts as a BMP (bone morphogenetic protein) scavenger that promotes 'BMP resistance' in pathological conditions 2. In cancer cachexia, ERFE is upregulated in skeletal muscle through STAT3-driven expression, contributing to muscle wasting by interfering with BMP-Smad1/5/8 signaling pathways 2. The protein also demonstrates significant clinical relevance as a prognostic biomarker across multiple cancer types, with aberrant expression observed in 22 tumor types and prognostic impact in 11 cancer types 3. ERFE expression correlates with oncogenic mutations, higher tumor mutational burden, and influences intratumoral immune cell infiltration, suggesting broader roles in tumorigenesis beyond its established iron regulatory functions 3.