In contrast, lack of functional folliculin, as observed in Birt-Hogg-Dubé syndrome, leads to hyperactivation of mTORC1-mediated phosphorylation of S6 kinase and 4E-BP1, but not of TFEB, which translocates to the nucleus when not phosphorylated and induces transcription of Rag C/D GTPases, further stimulating mTOR signaling activity30. Here, MTOR is linked to Birt-Hogg-Dube syndrome.