✓a tumor suppressor possessing a ubiquitin ligase activity and also serving as an adaptor protein for signaling regulators in a ubiquitin ligase activity-independent manner [201,202]✓activates the PI3K/AKT/mTOR/S6K pathway by direct binding to PI3K p110 [160]✓VHL-KD downregulates p-RPS6 (S235/236) in HEK293 cells [160]. The gene discussed is PIK3CB; the disease is neoplasm.