TPD52 is a multifunctional protein with context-dependent roles in cancer progression. Canonically identified as an oncogene frequently amplified at chromosome 8 across multiple cancer types including ovarian, breast, and gastric cancers 12, TPD52 overexpression correlates with poor clinical outcomes 3. However, recent evidence reveals TPD52 functions as a tumor suppressor in bladder cancer through endoplasmic reticulum (ER) stress regulation 4. Mechanistically, TPD52 operates through multiple pathways: (1) promoting ATF6 cleavage to modulate ER stress and unfolded protein response signaling, regulated by APC/Cdc20-mediated proteolysis 4; (2) inhibiting AMPK kinase activity to dysregulate energy metabolism 3; (3) enhancing lipid storage via lipophagy to protect against ferroptosis 5; and (4) activating PI3K/AKT/mTOR signaling in gastric cancer 6. TPD52's dual oncogenic and tumor-suppressive roles suggest its function is cancer-type and pathway-context dependent. Its broad overexpression across malignancies and potential as an immunotherapeutic target 7 make it a promising biomarker. The protein's involvement in fundamental cellular processes—calcium binding, protein homodimerization, and secretion—underscores its broad regulatory significance in cancer biology.