HJV (hemojuvelin) functions as a bone morphogenetic protein (BMP) coreceptor that enhances BMP signaling to regulate hepcidin (HAMP) expression and maintain iron homeostasis 1. As a signaling molecule expressed in the liver, HJV senses iron accumulation and participates in the complex regulatory pathways that control hepcidin, the iron regulatory hormone 2. Hepcidin, in turn, regulates ferroportin activity to control iron entry into the bloodstream and prevent systemic iron overload 3. Mutations in HJV cause juvenile hemochromatosis type 2A (JH2A), a severe autosomal recessive disorder characterized by rapid, multi-organ iron accumulation 4. Unlike the common HFE-associated hemochromatosis, HJV mutations produce early-onset disease affecting both sexes equally, with iron deposition in cardiac, hepatic, endocrine, and other parenchymal tissues 4. Though HJV mutations are rare, they are more central to iron homeostasis than HFE and represent important models for understanding iron trafficking mechanisms 5. Clinical recognition of HJV-related hemochromatosis requires genetic testing and is critical for early intervention with aggressive iron chelation therapy to prevent organ dysfunction and potentially avoid transplantation 4.