EYA2 is a dual-function protein with both tyrosine phosphatase and transcriptional coactivator activities. As a transcriptional coactivator, it partners with SIX1 and other SIX family members to regulate gene expression during organogenesis, particularly in skeletal myogenesis 1. As a histone phosphatase, EYA2 dephosphorylates histone H2AX at tyrosine-142, promoting DNA repair through recruitment of MDC1-containing complexes and protecting cells from apoptosis during genotoxic stress. Clinically, EYA2 displays context-dependent roles in cancer. In hepatocellular carcinoma, EYA2 functions as a tumor suppressor by transcriptionally regulating SOCS3 to inhibit JAK/STAT signaling; reduced EYA2 expression correlates with poor prognosis 2. Conversely, EYA2 is overexpressed and pro-tumorigenic in prostate cancer, promoting proliferation, invasion, and docetaxel resistance via AKT/Bcl-2 signaling 3. In Group 3 medulloblastoma, EYA2 is essential for MYC-dependent tumor growth, and its phosphatase activity inhibition reduces MYC expression and prevents progression 4. Similarly, in glioblastoma stem cells, EYA2 localization at centrosomes drives mitotic spindle assembly; its inhibition induces mitotic catastrophe 5. In lung cancer, EYA2 phosphatase activity selectively controls migration and invasion without affecting cell survival, identifying it as a potential antimetastatic target 6.