PDGFA (platelet-derived growth factor subunit A) is a potent mitogen for mesenchymal cells that regulates embryonic development, cell proliferation, migration, and survival 1. The protein functions through both canonical PDGFRA-dependent signaling and alternative pathways; notably, in glioblastoma, EPHA2 acts as an alternative receptor that mediates PDGFA activity independently of PDGFRA, activating PI3K-AKT signaling 2. PDGFA is critical for normal organogenesis, including lung alveolar septum formation, gastrointestinal development, and oligodendrocyte myelination, with expression modulated by alternative splicing generating functional variants 3. In disease contexts, PDGFA contributes significantly to glioblastoma progression through GOLM1-mediated AKT activation 4 and induces defective mitosis in neural progenitor cells, promoting chr7 instability and transformation 5. PDGFA is actively enriched in tumor-derived exosomes from colorectal cancer patients, particularly in cancer stem cell populations, suggesting roles in metastasis 6. In epilepsy, microglial GPR35-mediated stabilization of PDGFA domain 2 suppresses neuroinflammation and seizures via PI3K-AKT signaling 7. Clinically, PDGFA expression patterns serve as diagnostic biomarkers for connective tissue disease-related interstitial lung disease, with differential expression distinguishing disease subtypes and predicting prognosis 8. Combined PDGFRA and EPHA2 inhibition shows promise for overcoming therapeutic resistance in glioblastoma.