PTPN18 is a protein tyrosine phosphatase that functions primarily as a tumor suppressor across multiple cancer types, though context-dependent oncogenic roles exist. As a non-receptor tyrosine phosphatase, PTPN18 dephosphorylates specific tyrosine kinase substrates including HER2 and ETS1 12. The protein contains distinct functional domains: its catalytic domain dephosphorylates phosphorylated substrates, while its PEST domain promotes ubiquitin-mediated degradation pathways 1. In breast cancer, PTPN18 suppresses metastasis through nuclear translocation via MVP and importin β2, where it dephosphorylates ETS1 and inhibits TGF-β signaling and epithelial-to-mesenchymal transition 2. PTPN18 also functions as a tumor suppressor by promoting cyclin E degradation via the ubiquitin-proteasome pathway, causing cell cycle arrest and apoptosis 3. In endometrial cancer, PTPN18 knockdown inhibits proliferation and metastasis while promoting apoptosis 4. Additionally, PTPN18 interacts with fibrillarin to regulate MAPK signaling and rRNA methylation 5. In hepatocellular carcinoma, PTPN18 acts as a tumor suppressor by activating p53 signaling while suppressing AKT/FOXO1 cascades, with HBx protein repressing its expression 6. However, in glioblastoma, PTPN18 displays oncogenic properties, correlating with CD8+ T cell exhaustion and immune suppression 7. These findings suggest PTPN18 as a potential therapeutic target across multiple malignancies.