TPTE2 (transmembrane phosphoinositide 3-phosphatase and tensin homolog 2) is a PTEN homolog localized to the endoplasmic reticulum, Golgi membrane, and cytosol. Despite structural similarity to PTEN, TPTE2 shows no intrinsic phosphoinositide phosphatase activity [UniProt], though GO annotations suggest involvement in phosphatidylinositol-3,4,5-trisphosphate and phosphatidylinositol-3,4-bisphosphate 3-phosphatase activities. TPTE2 has emerged as a disease-relevant gene in multiple contexts. Variants in TPTE2 have been identified as novel candidate genetic factors in severe sperm motility disorders (immotile or near-immotile sperm), suggesting a role in flagellar function 1. Genetic variants near TPTE2 associate with persistent cervical high-risk HPV infections, with expression enriched in the endocervix 2, and TPTE2 variants show significant association with hepatocellular carcinoma susceptibility through immune response pathways 3. Functionally, TPTE2 can partially compensate for PTEN loss, normalizing cancer-associated phenotypes including accelerated wound healing, increased proliferation, and reduced apoptosis in epithelial cells 4. These findings suggest TPTE2 functions as a PTEN-like regulator in cellular processes beyond canonical phosphatase activity, with potential therapeutic implications for PTEN-deficient cancers.