In seizure disorders such as TSC and NPC that are characterized by autophagy dysregulation (Pacheco et al., 2009; Caccamo et al., 2013), increase in normal tau levels may in turn contribute to both seizure activity and PTEN inhibition, creating a feedback loop of mTOR overactivation that results in further hyperphosphorylation of tau (Figure 3). Here, PTEN is linked to epilepsy.