THBS2 (thrombospondin 2) encodes an adhesive glycoprotein that serves as a critical mediator of extracellular matrix interactions and immune regulation in disease pathogenesis. THBS2 is predominantly expressed by cancer-associated fibroblasts (CAFs) and functions as a key orchestrator of tumor microenvironments 12. The protein operates through multiple receptor-mediated pathways, including binding to CD36 for antiangiogenic effects, CD47 to activate MAPK/ERK5 signaling promoting tumor progression 3, and TLR4 to stimulate FAK/TGF-β pathways in hepatic stellate cell activation 4. THBS2+ CAFs create immunosuppressive niches that facilitate therapeutic resistance, particularly to immune checkpoint blockade and oxaliplatin chemotherapy 15. Clinically, THBS2 serves as a robust biomarker across multiple diseases: elevated expression predicts poor survival in early-stage lung adenocarcinoma 2, correlates with advanced liver fibrosis and NASH progression 64, and distinguishes tumors from normal tissues with high sensitivity and specificity in extracellular vesicle-based cancer detection 7. The protein's secretion via exosomes enables its detection in plasma as a liquid biopsy marker 2. THBS2's role in promoting epithelial-mesenchymal transition and drug resistance makes it an attractive therapeutic target for multiple cancer types and fibrotic diseases.