EMP2 (epithelial membrane protein 2) is a ~160 amino acid cell surface protein encoded by the PMP22 gene family that functions as a multifaceted regulator of cell membrane protein trafficking and cellular processes. Primary functions include regulating plasma membrane expression of integrins (ITGA6-ITGB1, ITGA5-ITGB3, ITGA5-ITGB1), MHC1, and ICAM1, thereby modulating cell-matrix adhesion and immune surveillance 1. Mechanistically, EMP2 activates focal adhesion kinase (FAK) and regulates PTK2/SRC signaling pathways, controlling cell migration, contraction, and proliferation 2. EMP2 promotes angiogenesis via VEGFA upregulation through HIF1A-dependent pathways and regulates cancer stem cell self-renewal through HIF-1α upregulation 3. In hepatocellular carcinoma, EMP2 enhances invasive capacity through dual regulation of autophagy and integrin signaling 4. Clinically, EMP2 is significantly upregulated in invasive breast and hepatocellular carcinomas, correlating with poor prognosis 34. EMP2 serves as a biomarker in cancer-associated fibroblasts' prognostic signatures for breast cancer outcomes 5. Anti-EMP2 therapeutic strategies show promise: granzyme B fusion proteins targeting EMP2 demonstrate cytotoxicity in triple-negative breast cancer and immune microenvironment remodeling 6, while anti-EMP2 antibodies reduce pathological cell contraction in proliferative vitreoretinopathy 2. EMP2 mutations associate with nephrotic syndrome 10, indicating roles in renal filtration. Overall, EMP2 represents a context-dependent therapeutic target, particularly in cancer and immune-mediated diseases 1.