STRN3 (striatin 3) is a calmodulin-binding scaffolding protein that serves as the central component of STRIPAK (striatin-interacting phosphatase and kinase) complexes 1. As a regulatory subunit of protein phosphatase 2A (PP2A), STRN3 recruits and dephosphorylates MST1/2 kinases, thereby suppressing Hippo tumor-suppressor pathway activity and promoting YAP nuclear translocation 2. STRN3 also interacts with MAP4K4 to regulate cell invasion through VASP phosphorylation while coupling MAP4K4 to PP2A-mediated growth inhibition 3. STRN3 is significantly upregulated in multiple cancers including gastric, hepatocellular, and esophageal squamous cell carcinomas, correlating with poor prognosis and YAP activation 245. STRN3 knockdown inhibits cancer cell proliferation and migration 4. In lung adenocarcinoma, STRN3 interacts with TRAF3IP3 and facilitates ER stress-mediated apoptosis through the PERK/ATF4/CHOP pathway 6. A novel STRN3::PDGFRB fusion gene identified in acute myeloid leukemia exhibits transforming potential sensitive to tyrosine kinase inhibitors 7. Clinically, selective inhibitors targeting the STRN3-PP2A interaction or STRN3-MST1/2 interaction, including the peptide SHAP and compounds like disulfiram, reactivate Hippo signaling and enhance chemotherapy sensitivity 28.