Folliculin (FLCN)

Folliculin is a highly conserved multifunctional protein with a key role in tumor suppression and homeostatic signaling, forming complexes with FNIP1 and FNIP2 and modulating AMPK and mTORC1 pathways. Loss-of-function mutations in FLCN cause autosomal dominant Birt-Hogg-Dubé syndrome, leading to renal neoplasia, skin papules (fibrofolliculomas), and pulmonary cysts. Structural studies show folliculin sharing features with DENN domain proteins, functioning as a GAP for Rag GTPases, thereby regulating lysosomal recruitment of mTORC1, autophagy, and transcription factors (TFEB/TFE3). Additional roles are described in cytoskeletal dynamics, cell adhesion, cell cycle control, and mitochondrial biogenesis. Interruption of folliculin activity drives cellular dysregulation and tumor predisposition, but no targeted therapies or direct inhibitors of FLCN are currently in clinical use.

Other names

Birt-Hogg-Dubé syndrome proteinBHD proteinDENND8BFLCLMGC17998MGC23445BHD skin lesion fibrofolliculoma proteinb/hd syndrome proteinfolliculin interacting protein partner

Drugs that modulate mTORC1 (e.g., mTOR inhibitors like rapamycin) may functionally intersect with FLCN downstream effects. No direct FLCN-targeting mechanisms currently established for approved therapies.