PTPRO is a receptor protein tyrosine phosphatase with multifaceted roles in cell regulation and disease suppression. As a phosphatase, PTPRO dephosphorylates key signaling proteins including VCP/p97 1, JAK2 2, and STAT3 3, thereby modulating critical intracellular pathways. In neural development, PTPRO serves as a specific surface marker of midbrain dopaminergic progenitors and predicts successful neuronal differentiation 4. It also functions in spinal cord injury recovery by promoting anti-inflammatory M2 microglial polarization through NF-κB/STAT6 pathway inhibition 5. PTPRO exhibits robust tumor suppressor activity across multiple cancer types. In hepatocellular carcinoma, hepatic methylation-mediated PTPRO silencing promotes tumorigenesis 1. In renal cell carcinoma, reduced PTPRO expression correlates with poor prognosis and diminished immune infiltration 6. Similarly, in lung cancers (adenocarcinoma and squamous cell carcinoma), PTPRO suppresses progression via mitochondria-dependent apoptosis and epithelial-to-mesenchymal transition inhibition 37. In breast cancer, PTPRO represses lung metastasis by inhibiting JAK2-YAP signaling 2. Additionally, PTPRO marks cancer stem-like cells associated with organ-specific colorectal cancer metastasis 8. Clinically, PTPRO methylation and reduced expression emerge as independent prognostic biomarkers across cancers, with restoration of PTPRO expression representing a potential therapeutic strategy for multiple malignancies.