NEO1 is composed of 4 N-terminal immunoglobulin-like domains, followed by 6 fibronectin type III–like domains, a single transmembrane helix, and an intracellular domain. Interactions between neogenin and HJV are mediated by fibronectin domains 5 and 6 of neogenin. Two HJV molecules act as molecular staples to bring together the juxtamembrane regions of 2 NEO1 receptors.²  The binding of HJV to NEO1 on the plasma membrane is essential for systemic iron homeostasis and triggers the γ-secretase–like protease cleavage of NEO1 to delete its cytoplasmic domain. This cleavage prevents the degradation of truncated NEO1, leading to its accumulation on plasma membrane. The consequence is an activation of BMP signaling and the transcription of the hepcidin gene by a mechanism that still needs to be clarified. Because HJV is also a coreceptor for BMPs, the NEO1/HJV complex could act as a shuttle for BMP ligands.