PTPN14 is a non-receptor protein tyrosine phosphatase that functions as a tumor suppressor through negative regulation of Hippo pathway signaling. It dephosphorylates and inactivates YAP1, a transcriptional coactivator that drives cell proliferation and stemness, thereby restraining oncogenic signaling in a cell density-dependent manner. Beyond Hippo regulation, PTPN14 mediates beta-catenin dephosphorylation at adhesion junctions and regulates TGF-beta expression, supporting roles in cell-cell adhesion, migration, and epithelial-mesenchymal transition. PTPN14 dysfunction is associated with multiple cancer types. Loss-of-function variants confer substantial risk of basal cell carcinoma in the germline setting (OR 8.0), with over half of carriers developing BCC in their lifetime, and also elevate cervical cancer risk (OR 12.7) 1. Somatic PTPN14 mutations occur in 23% of skin BCCs 2, while downregulation is observed in triple-negative breast cancer and osteosarcoma, where it inversely correlates with aggressive phenotypes 3 4. High-risk HPV oncoproteins degrade PTPN14 to promote YAP1 activation and inhibit keratinocyte differentiation, contributing to HPV-driven carcinogenesis 5 6. Recent therapeutic approaches target PTPN14 restoration: mRNA-lipid nanoparticle delivery of PTPN14 inhibits tumor growth and metastasis in triple-negative breast cancer models 3, while fenofibrate, a clinically approved lipid-lowering agent, enhances anti-tumor effects by stabilizing PTPN14 and promoting YAP cytoplasmic sequestration 7. Small-molecule inhibitors of the HPV E7–PTPN14 interaction show antitumoral activity against HPV-positive cervical cancer cells 8.