Folliculin

Folliculin is a protein expressed in a number of normal tissues such as skin, lung and kidney. Its exact function remains unknown. Folliculin is the product of the FLCN gene. This is located in the Smith-Magenis syndrome region on chromosome 17. Mutations in this gene are associated with Birt-Hogg-Dubé syndrome, which is characterized by fibrofolliculomas, renal tumors, lung cysts, and pneumothorax.

Recent evidence suggests that FLCN acts as a tumor suppressor via an interaction with the mTOR energy processing pathway, and its absence contributes to the development of BHDS-associated renal tumors.

Folliculin mutations are associated with Birt-Hogg-Dubé syndrome, which is characterized by fibrofolliculomas, renal tumors, lung cysts, and pneumothorax. A number of mutations are known, including deletions, substitutions, and duplications, which are thought to lead to protein shortening and consequent loss of function

There may be subtypes of Birt-Hogg-Dubé syndrome, as lung cysts are the predominant feature in some families and skin and kidney manifestations are less common. In addition, mutations may be specific to certain ethnicities, as Japanese and Caucasian patients have been found to have different mutation distributions and unique alterations.

1. Baba M et al. (2006) Folliculin encoded by the BHD gene interacts with a binding protein, FNIP1, and AMPK, and is involved in AMPK and mTOR signaling. Proc Natl Acad Sci U S A 103:15552-15527.
2. Lawrence RE et al (2019) Structural mechanism of a Rag GTPase activation checkpoint by the lysosomal folliculin complex. Science 366:971-977.
3. Mathieu J et al (2019) Folliculin regulates mTORC1/2 and WNT pathways in early human pluripotency. Nat Commun 10:632.
4. Woodford MR et al (2021) The tumor suppressor folliculin inhibits lactate dehydrogenase A and regulates the Warburg effect. Nat Struct Mol Biol 28:662-670.