PTP4A2 (protein tyrosine phosphatase 4A2) is a member of the Phosphatase of Regenerative Liver (PRL) family that functions as an oncogenic driver across multiple cancer types. Mechanistically, PTP4A2 operates through dephosphorylation-dependent signaling axes; in glioblastoma, it modulates the ROBO1 pathway to promote self-renewal and tumorigenicity 1, while in hepatocellular carcinoma it contributes to proliferation, migration, and invasion 2. Beyond intrinsic tumor cell functions, PTP4A2 significantly impacts the tumor microenvironment, with deletion increasing apoptosis and proinflammatory signals while reducing immunosuppression in glioblastoma models 3. In normal physiology, PTP4A2 regulates vascular development through VEGF-A and DLL-4/NOTCH-1 signaling, controlling endothelial cell migration and sprouting angiogenesis 4. Disease relevance is substantial: high PTP4A2 expression correlates with poor prognosis in gliomas and hepatocellular carcinoma 32. Clinically, PTP4A2 represents a therapeutic target; pharmacological inhibition via pan-PTP4A inhibitors like JMS-053 suppresses tumor growth 3, and ROBO1-targeted CAR T cell therapy exploiting PTP4A-ROBO1 dependency doubled survival in recurrent glioblastoma models 1. However, compensatory mechanisms among PTP4A family members may limit selective PTP4A2 inhibition 5.