Repulsive guidance molecule b (RGMb)

Repulsive guidance molecule b (RGMb), also known as DRAGON, is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein and member of the repulsive guidance molecule family. RGMb functions primarily as a co-receptor for bone morphogenetic proteins (BMPs), specifically BMP2 and BMP4, enhancing their signaling at the membrane level and influencing processes such as embryonic development, axonal guidance, immune regulation, and tumorigenesis[1][3][5]. Structurally, RGMb lacks a transmembrane domain, instead anchoring to the plasma membrane via a GPI lipid modification. RGMb binds to BMPs and to the receptor Neogenin (NEO1), playing a critical role in forming and stabilizing signaling complexes. It is also involved in immune modulation via direct interaction with programmed death-ligand 2 (PD-L2). Dysfunction or altered expression of RGMb has been implicated in diseases including cancer, neurodegenerative disorders, and systemic iron metabolism conditions. Despite its centrality in various signaling pathways, its complete physiological and pathological roles are still being elucidated, and there are no approved drugs directly targeting RGMb as of the latest research[1][3][5].

Other names

DRAGONrepulsive guidance molecule BMP co-receptor brepulsive guidance molecule family member bRGMB

Acts as a co-receptor to potentiate BMP signaling (enhances signaling for BMP2/BMP4; inhibits GDF5 signaling); Bridges Neogenin (NEO1) and BMP2 or other BMP ligands, stabilizing receptor complexes; Interacts with programmed death-ligand 2 (PD-L2), modulating immune responses[1][5][6].