Taken our evidences together, our results unveiled new conceptual and functional avenues in GBM, with potential clinical implications, by demonstrating that SF3B1 is an attractive therapeutic target in GBM since its inhibition impaired key pathophysiological processes in GBM -biology (i.e., proliferation/migration/tumorspheres formation/apoptosis, etc.)likely by modulating different oncogenic signaling pathways (AKT-mTOR/ß-catenin) associated with GBM survival/initiation/progression, and an imbalance of BCL2L1 splicing. Here, AKT1 is linked to glioblastoma.