RHEB and tuberous sclerosis: Rapamycin and its analogs, that are currently in clinical use to treat epilepsy in TSC patients, curbed epileptiform activity in mouse models harboring TSC1/2, RHEB, MTOR, or PTEN mutations when administered long-term (>7-day) (Curatolo and Moavero, 2013; Lasarge and Danzer, 2014; Crino, 2016; Kim and Lee, 2019; Stafstrom, 2019; Hsieh et al., 2020).