{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPEBP1, also known as Raf kinase inhibitory protein (RKIP), functions as a dynamic scaffold that integrates and modulates key signal‐transduction pathways. In non–cancer contexts, PEBP1 directly complexes with enzymes such as 15‐lipoxygenase (15LO1/15LO2) to alter substrate specificity, thereby promoting the oxygenation of phosphatidylethanolamines and triggering ferroptotic cell death when antioxidant defenses (e.g., GPX4) are inadequate. In human airway epithelial cells, these PEBP1‐15LO complexes additionally engage in reciprocal interactions with autophagic machinery, balancing pro–ferroptotic signals with cellular survival pathways that are critical in inflammatory conditions such as asthma, as well as in kidney failure and brain injury."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn neoplastic settings, PEBP1 operates as a master regulator of oncogenic signaling and a potent metastasis suppressor. By inhibiting the Raf/MEK/ERK cascade, NF‑κB signaling, and other pathways (including G protein–coupled receptor and GSK3β routes), its expression is closely associated with reduced tumor invasiveness, diminished epithelial–mesenchymal transition and improved responses to apoptosis‐inducing chemotherapeutics. A broad spectrum of studies in breast, prostate, colorectal, ovarian, hepatocellular, gastric, cervical, renal, and pancreatic cancers demonstrates that downregulation of PEBP1 correlates with accelerated cell cycle progression, enhanced chemoresistance, increased metastatic dissemination, and a poorer clinical outcome. Furthermore, PEBP1 expression influences the tumor microenvironment by modulating chemokine production and the recruitment of tumor‐associated macrophages, while its levels in tissue and even bodily fluids (such as urine) show promise as diagnostic and prognostic biomarkers."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "37"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in cell survival and metastasis suppression, PEBP1 exquisitely regulates cell cycle kinetics, mitotic checkpoint fidelity and cellular differentiation. Its conserved, highly dynamic ligand‐binding pocket serves as an integration hub for regulatory inputs—where phosphorylation events and small–molecule ligand binding cooperatively modulate its association with target kinases such as Raf-1. Such molecular tuning governs downstream MAPK activation, influencing vital processes including mitotic progression, apoptotic sensitivity and cell motility. Moreover, PEBP1 has been implicated in promoting neuronal differentiation and modulating cardiac contractility, underscoring its broad impact on diverse physiological and pathological states."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "38", "end_ref": "41"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jinming Zhao, Valerie B O'Donnell, Silvana Balzar, et al. 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