RHEB and cancer: Mutations in other components of this pathway, including inactivating mutations in DEPDC5, NPRL2, and NPRL3, and an activating mutation (Y35N) in RHEB have been shown to lead to strong mTORC1 activation in vitro, including analysis of cancer cell lines in some cases (Bar-Peled et al., 2013, Grabiner et al., 2014).