Disruption of mTOR signaling due to variants in its repressors such as TSC1, TSC2, DEPDC5, PTEN or in its activators such as RHEB, and MTOR lead to a set of disorders characterized by early onset and often drug-resistant epilepsies called mTORopathies (Lipton and Sahin, 2014; Moloney et al., 2021). Here, RHEB is linked to epilepsy.