PDGFD (platelet-derived growth factor D) is a growth factor that mediates cell proliferation, migration, and survival primarily through PDGFRB receptor signaling 1. It activates key intracellular pathways including phosphatidylinositol 3-kinase/protein kinase B and ERK1/2 cascades, supporting mesenchymal cell development and angiogenesis 2. PDGFD plays critical roles in tissue homeostasis: it regulates wound healing and vascular maturation during angiogenesis, while also supporting hematopoietic-immune development through osteoblast-mediated signaling 3. Dysregulation of PDGFD contributes to multiple pathological conditions. In liver fibrosis, elevated PDGFD expression by endothelial cells drives profibrotic responses through the GATA4/MYC/PDGFB/PDGFRβ axis 2. Conversely, PDGFD shows tumor-suppressive effects: higher PDGFD expression in non-metastatic osteosarcoma correlates with extended survival and inhibits metastasis through suppression of epithelial-mesenchymal transition 1. In keloids, reduced PDGFD levels associate with excessive skin fibrosis 4. PDGFD participates in mesenchymal neoplasia through fusion-driven mechanisms in dermatofibrosarcoma protuberans 5. Genetically, rare PDGFD variants associate with pulmonary arterial hypertension (PAH), a vasculopathy characterized by pathogenic pulmonary arterial remodeling, though PDGFD variants show limited evidence for PAH causality compared to definitive PAH genes 67. These findings establish PDGFD as a pleiotropic regulator with context-dependent pro- and anti-pathogenic roles.