Hemojuvelin (HJV)

Class

Anti-hemojuvelin monoclonal antibody

Pathway

Blocks BMP (bone morphogenetic protein) signaling -> suppresses hepcidin -> hepcidin/iron-restricted erythropoiesis pathway (anemia of myelofibrosis/CKD)

Hemojuvelin (HJV) is a protein anchored on the surface of liver cells that acts as a co-receptor for bone morphogenetic proteins (BMPs), signaling molecules that regulate iron metabolism. When BMPs engage HJV and its partner receptors, an intracellular cascade (the BMP-SMAD pathway) switches on production of hepcidin, the body's master iron-regulatory hormone. Hepcidin works by degrading ferroportin, the channel that exports iron from intestinal cells, macrophages, and liver stores into the bloodstream. In chronic inflammatory or marrow disorders such as myelofibrosis and chronic kidney disease, hepcidin production becomes excessive, trapping iron inside storage cells and starving the bone marrow of the iron needed to build red blood cells. This produces a form of anemia driven not by iron deficiency itself but by iron being inaccessible - so-called iron-restricted erythropoiesis. Antibodies that block HJV interrupt BMP signaling at its source, lowering hepcidin output, allowing ferroportin to remain active, and freeing iron for red blood cell production. This mechanism is being explored broadly across diseases where elevated hepcidin drives anemia, offering an alternative to approaches that simply supply more iron or stimulate red cell production directly.