RGMA (repulsive guidance molecule BMP co-receptor a) is a multifunctional protein with roles in neural development and immune regulation. In the nervous system, RGMA acts as a neurite growth inhibitor by binding its receptor neogenin (NEO1) to activate RHOA-ROCK1 signaling and inhibit neuronal growth cone extension 1. RGMA also functions as a bone morphogenetic protein co-receptor, signaling through SMAD pathways. Beyond its classical neuronal roles, RGMA participates in metabolic regulation and immune responses. Following ischemic-reperfusion injury, RGMA knockdown shifts neuronal metabolism toward oxidative phosphorylation, protecting against tissue damage by inhibiting glycolytic flux through PGK1 regulation 2. In neuromyelitis optica, RGMA signaling in macrophages drives neutrophil-related inflammation; anti-RGMA antibodies ameliorate astrocytopathy and neuropathic pain 3. Clinically, RGMA functions as a tumor suppressor across multiple cancer types. In breast cancer, RGMA promoter hypermethylation silences expression, with restoration by demethylating agents blocking tumor growth via FAK/Src/PI3K/AKT pathway inhibition 4. In esophageal cancer, reduced RGMA expression correlates with poor prognosis and facilitates cancer-associated fibroblast differentiation 5. RGMA also appears dysregulated in endometrial cancer subtypes 6, suggesting broad tumor-suppressive function across tissues.