Further analysis revealed that depletion of DCAF1 or treatment with MLN4924 does not affect mTOR hyperactivation in <i>NF2</i>-mutant tumor cells, suggesting that loss of Merlin activates mTOR independently of CRL4<sup>DCAF1</sup> Intriguingly, combining MLN4924 with the mTOR/PI3K inhibitor GDC-0980 suppresses the growth of <i>NF2</i>-mutant tumor cells <i>in vitro</i> as well as in mouse and patient-derived xenografts.