EMP1 (epithelial membrane protein 1) is a tetraspan membrane protein with context-dependent roles in cancer biology and normal tissue homeostasis. In normal physiology, EMP1 is essential for epithelial tight junction formation through SOS1/Ras/MEK/ERK signaling in airway epithelium 1 and safeguards hematopoietic stem cells by suppressing sphingolipid metabolism and mitigating endoplasmic reticulum stress via interaction with ceramide synthase 2 2. In cancer, EMP1 functions context-dependently as either a tumor promoter or suppressor 3. In colorectal cancer, EMP1 marks high-relapse residual tumor cells that cause metastatic recurrence; genetic ablation of EMP1-high cells prevents metastatic relapse after surgery 4. In triple-negative breast cancer, EMP1 promotes disease progression by mediating cancer-associated fibroblast infiltration through IL-6 secretion via NF-κB signaling 5. Conversely, in bladder cancer, EMP1 downregulation promotes metastasis by activating PPAR-gamma signaling, enhancing migration and conferring ferroptosis resistance 6. EMP1 also serves as a biomarker for drug resistance in lung cancer and leukemia 3, and its editing in CD8+ T cells enhances immunotherapy efficacy against glioblastoma 7. These findings establish EMP1 as a promising but cancer-type-specific therapeutic target.