The mechanism of Phosphatidylethanolamine-Binding Protein 1 in Neuro-Related Diseases

Phosphatidylethanolamine-Binding Protein 1 (PEBP1), also known as Raf Kinase Inhibitory Protein (RKIP), is a widely expressed, highly conserved multifunctional signaling regulator that governs the activity of central signaling pathways including Mitogen-Activated Protein Kinase (MAPK), Nuclear Factor-κB (NF-κB) and G Protein-Coupled Receptors (GPCRs). We note that recent research has uncovered its role as a critical ferroptosis regulator, showing remarkably specific expression and function across different diseases. Here we systematically review the structure and function of PEBP1, focusing on its core mechanisms as a molecular hub in various neurological disorders. We also systematically integrate PEBP1's multiple roles across these disorders and explain its key position within neuropathological networks by coupling classical signaling pathways with the ferroptosis program. We further examine intervention strategies targeting its functional states and protein interaction networks, and then discuss its clinical translational potential as a therapeutic target, hoping to provide insights for investigations into disease-related mechanisms and the development of therapeutic strategies.Clinical trial number: not applicable.