PROTAC mediated FKBP12 degradation enhances Hepcidin expression via BMP signaling without immunosuppression activity

Dear Editor,Hepcidin is a 25-amino acid peptide acting as a pivotal negative regulator in iron homeostasis,which can bind to an iron exporter,ferroportin 1,and induce its internalization and degradation.1 Hepcidin is produced in hepatocytes mainly under the control of BMP signaling.BMP2/6,secreted by liver endothelial cells in response to iron level,binds to BMP type I and type II receptors and triggers the phosphorylation of Smad1/5/8 which directly promotes hepcidin expression.1 The immunophilin family protein FKBP12 is associated with BMP type I receptors to prevent uncontrolled receptor activation.