STRN4 (striatin 4) is a calmodulin-binding scaffolding protein that serves as the central component of STRIPAK (striatin-interacting phosphatase and kinase) complexes 1. These complexes regulate protein (de)phosphorylation and control multiple signaling pathways including Hippo, MAPK, and nuclear receptor signaling 1. STRN4 functions as a key negative regulator of the Hippo pathway by facilitating PP2A-mediated dephosphorylation of MAP4K kinases, thereby stabilizing YAP/TAZ and antagonizing pathway activation 12. Mechanistically, STRN4 undergoes dynamic post-translational modification; DHHC9-mediated palmitoylation of STRN4 at cysteine 701 reduces YAP phosphorylation and promotes its nuclear translocation, activating downstream Hippo targets 3. Energy stress reduces MAP4K2 association with STRN4-containing STRIPAK complexes, promoting autophagy through MAP4K2-mediated LC3A phosphorylation 4. Clinically, STRN4 dysregulation is implicated in multiple cancers. STRN4 depletion suppresses cancer cell proliferation, migration, and invasion while increasing chemotherapy sensitivity 5. In hepatocellular carcinoma, epigenetic silencing of STRN4 drives tumorigenicity 6. Additionally, STRN4 localizes to dendritic spines where it maintains mushroom spine morphology through PP2A interaction, suggesting relevance to neurodevelopmental disorders 7.