PDGFD encodes a platelet-derived growth factor that functions as a potent mitogen for mesenchymal cells and plays essential roles in embryonic development, cell migration, proliferation, and angiogenesis. The protein operates through binding to platelet-derived growth factor receptors and activates downstream signaling cascades including PI3K/AKT and ERK1/2 pathways. PDGFD also promotes wound healing and regulates immune cell recruitment and vessel maturation during angiogenic processes. In disease contexts, PDGFD has been implicated in multiple pathological conditions. In cholangiocarcinoma, tumor-derived PDGFD stimulates cancer-associated fibroblasts to produce VEGF-C and VEGF-A, promoting lymphatic vascularization and early metastatic spread; this axis can be blocked by PDGFRβ inhibition with imatinib or by inducing fibroblast apoptosis 1. Conversely, in osteosarcoma, higher PDGFD expression correlates with reduced metastatic potential, suggesting an inhibitory effect on epithelial-mesenchymal transition 2. Rare deleterious variants in PDGFD have been associated with pulmonary arterial hypertension (PAH), though genes with such limited evidence require cautious interpretation in genetic testing 3, 4. Additionally, PDGFD-rearranged fusions, particularly COL6A3::PDGFD and EMILIN2::PDGFD, occur in dermatofibrosarcoma protuberans with distinct clinicopathologic features 5. In keloid pathogenesis, PDGFD showed negative correlation with disease, suggesting potential therapeutic value as a suppressive target 6.