In addition, since PTEN may exert its cellular functions independent of the PIP3 signaling pathway, e.g., inhibiting phosphorylation of transcription factor ETS-2 through MAPK [51], it remains possible that PTEN may affect the pathogenesis of tauopathy by a mechanism other than regulating the phosphorylation status of tau, such as by affecting tau ubiquitination and degradation. Here, ETS2 is linked to tauopathy.