PTPN3 (protein tyrosine phosphatase non-receptor type 3) is a multifunctional enzyme that plays complex roles in cancer biology and immune regulation. The protein contains both FERM and PDZ domains and exhibits tyrosine phosphatase activity 1. PTPN3 functions as a tumor suppressor in some contexts, suppressing lung cancer cell invasiveness by dephosphorylating DAAM1 and counteracting Src-mediated actin polymerization 1. However, activating mutations in PTPN3 promote cholangiocarcinoma cell proliferation and migration, with over 40% of intrahepatic cholangiocarcinomas containing somatic PTPN3 mutations 2. These gain-of-function mutations are associated with increased tumor recurrence rates 2. In breast cancer, PTPN3 is overexpressed and correlates with poor clinicopathological features 3. The protein also functions as an immune checkpoint in activated lymphocytes, with expression regulated by NFκB and TGFβ pathways 4. PTPN3's PDZ domain is targeted by high-risk human papillomavirus E6 proteins, contributing to viral oncogenesis 5. Pan-cancer analysis reveals PTPN3 as a prognostic biomarker associated with tumor immune microenvironment modulation and immunotherapy response prediction 6.