PTGFRN (prostaglandin F2 receptor inhibitor) is a transmembrane immunoglobulin superfamily protein that functions as a scaffold for extracellular vesicle engineering and a key driver of oncogenic signaling. Originally characterized as an inhibitor of prostaglandin F2-alpha receptor signaling, PTGFRN has emerged as a critical regulator of cancer progression across multiple tumor types. Mechanistically, PTGFRN promotes cancer cell proliferation, migration, and invasion through multiple pathways. In glioblastoma, PTGFRN activates pro-survival signaling via AKT and PI3K p110β, enhancing DNA damage repair and promoting radiation resistance 1. PTGFRN also regulates autophagy and directly binds integrin β1 and E-cadherin, facilitating metastatic-like phenotypes 2. Beyond cancer biology, PTGFRN serves as a scaffold protein preferentially sorted into extracellular vesicles, enabling high-density surface display of therapeutic molecules 3. Clinically, PTGFRN is significantly overexpressed across diverse cancers including glioblastoma, mesothelioma, and medulloblastoma, correlating consistently with poor prognosis 4, 5, 6. PTGFRN expression associates with immunosuppressive tumor microenvironments, reduced CD8+ T cell infiltration, and increased cancer-associated fibroblasts 6. These findings establish PTGFRN as both a prognostic biomarker and therapeutic target, with antibody-drug conjugates demonstrating efficacy in preclinical models 5.