TMEM88 is a transmembrane protein that primarily functions as an inhibitor of canonical Wnt/β-catenin signaling 1. The protein localizes to the cell membrane and cytoplasm, where it interacts with Dishevelled (DVL) to suppress Wnt pathway activation 12. TMEM88 also regulates TGF-β1/Smad signaling, inhibiting extracellular matrix accumulation and epithelial-mesenchymal transition in pleural fibrosis 3. Beyond cancer, TMEM88 functions as a developmental regulator of mesendodermal lineages and influences cardiovascular physiology, with loss-of-function models showing dysregulated arterial blood pressure 4. In cancer biology, TMEM88's role is context-dependent. In thyroid cancer, breast cancer, and hepatocellular carcinoma (HCC), TMEM88 acts as a tumor suppressor—overexpression suppresses proliferation and invasion while correlating with improved survival 56. However, in non-small cell lung cancer (NSCLC), cytosolic localization of TMEM88 promotes invasion and metastasis by activating p38-GSK3β-Snail signaling rather than inhibiting Wnt 2. Higher TMEM88 expression predicts better overall and disease-specific survival in HCC 6, and promoter methylation regulates TMEM88 expression in chemoresistance 7. These findings suggest TMEM88 is a promising therapeutic target in multiple cancers, though its subcellular localization critically determines its biological effects.