PTPN14 is a non-receptor protein tyrosine phosphatase functioning as a tumor suppressor through multiple regulatory pathways. Its primary function involves dephosphorylation of key signaling proteins at specific sites: it dephosphorylates PDGFRβ at Y692 to inhibit receptor activation 1, dephosphorylates breast cancer antiestrogen resistance 3 to suppress PI3K/AKT and ERK signaling 2, and phosphorylates YAP1 through LATS1 kinase to inhibit its oncogenic transcriptional activity 3 4. PTPN14 also mediates beta-catenin dephosphorylation at cell-cell adhesion junctions and promotes keratinocyte differentiation 5. Disease relevance is substantial across multiple cancer types. Loss-of-function PTPN14 variants confer high BCC predisposition (OR 8.0) and cervical cancer risk (OR 12.7) 6. Frequent PTPN14 mutations occur in basal cell carcinoma (23%) 7, and reduced expression enables anoikis resistance in triple-negative breast cancer 2. High-risk HPV E7 proteins specifically degrade PTPN14, promoting keratinocyte survival and oncogenic transformation independent of RB1 inactivation 5 4. Clinically, PTPN14 mRNA delivery via lipid nanoparticles effectively inhibits TNBC tumor growth and metastasis 2, and small-molecule inhibitors targeting HPV E7/PTPN14 interactions show antitumoral activity in cervical cancer 8.