Folliculin (FLCN) is a ~64 kDa protein. Multi-functional protein, involved in both the cellular response to amino acid availability and in the regulation of glycolysis. GTPase-activating protein that plays a key role in the cellular response to amino acid availability through regulation of the non-canonical mTORC1 signaling cascade controlling the MiT/TFE factors TFEB and TFE3. Activates mTORC1 by acting as a GTPase-activating protein: specifically stimulates GTP hydrolysis by RagC/RRAGC or RagD/RRAGD, promoting the conversion to the GDP-bound state of RagC/RRAGC or RagD/RRAGD, and thereby activating the kinase activity of mTORC1. The GTPase-activating activity is inhibited during starvation and activated in presence of nutrients. Acts as a key component for non-canonical mTORC1-dependent control of the MiT/TFE factors TFEB and TFE3, while it is not involved in mTORC1-dependent phosphorylation of canonical RPS6KB1/S6K1 and EIF4EBP1/4E-BP1. 1. Baba, M. et al. (2006) Proceedings of the National Academy of Sciences of the United States of America 103, 15552-7. PMID: 170281744. Petit, CS. et al. (2013) The Journal of cell biology 202, 1107-22. PMID: 240814916. Lawrence, RE. et al. (2019) Science (New York, N.Y.) 366, 971-977. PMID: 316729139. Woodford, MR. et al. (2021) Nature structural & molecular biology 28, 662-670. PMID: 3438124710. Jansen, RM. et al. (2022) Science advances 8, eadd2926. PMID: 36103527 | 
