PLXDC1 (plexin domain containing 1) is a transmembrane receptor protein that plays critical roles in angiogenesis and tumor biology. PLXDC1 functions as a cell-surface receptor for PEDF (Pigment Epithelium Derived Factor), forming homooligomers under basal conditions that dissociate upon PEDF binding to activate downstream signaling 1. The protein is essential for endothelial cell capillary morphogenesis and angiogenic processes 1. In cancer contexts, PLXDC1 demonstrates significant clinical relevance as a prognostic marker associated with poor outcomes across multiple tumor types. In colon cancer, high PLXDC1 expression correlates with advanced cancer stages, nodal metastasis, and shorter survival, while promoting cell viability, invasion, and macrophage polarization toward the immunosuppressive M2 phenotype via IL-6/STAT3 signaling 2. In glioblastoma, bevacizumab treatment upregulates PLXDC1, driving infiltrative tumor growth along perivascular spaces and reducing treatment efficacy 3. PLXDC1+ tumor-associated fibroblasts create desmoplastic, immunosuppressive microenvironments in pancreatic and bladder cancers, correlating with poor immunotherapy responses 45. Additionally, PLXDC1 serves as an entry receptor for rhesus monkey rhadinovirus, highlighting its role in viral pathogenesis 6. These findings establish PLXDC1 as a multifunctional protein central to angiogenesis, tumor progression, and therapeutic resistance.