GPR37 is a G protein-coupled receptor primarily expressed in oligodendrocytes and macrophages with multifaceted physiological roles. As a functional receptor, GPR37 binds multiple ligands including prosaposin, neuroprotectin D1 (NPD1), and osteocalcin, triggering downstream signaling via ERK phosphorylation and calcium mobilization 1. In immune responses, GPR37 activation in macrophages by NPD1 promotes phagocytosis and shifts cytokine production toward anti-inflammatory profiles, facilitating inflammatory pain resolution and sepsis protection 1. GPR37 regulates oligodendrocyte differentiation and CNS myelination through ERK1/2 pathway activation, modulating myelin stability 2. GPR37 exhibits dual roles in disease contexts. In neurodegenerative disease, the prosaposin-GPR37-IL-6 axis in oligodendrocytes drives neuroinflammation and dopamine neuron degeneration in Parkinson's disease, with GPR37 deficiency showing neuroprotection 2. Conversely, GPR37 activation by NPD1 or artesunate alleviates bone cancer pain by inhibiting osteoclastogenesis and neuronal hyperexcitability 3. In cancer contexts, GPR37 expression is paradoxically low in esophageal squamous cell carcinoma where restoration promotes radiosensitization through ATP1A1 ubiquitination 4, yet elevated in colorectal cancer liver metastasis where it promotes glycolysis and neutrophil recruitment 5. GPR37 misfolding accumulates in juvenile Parkinson's disease as a parkin substrate 6, indicating context-dependent neuroprotective versus pathogenic functions.