FLCN Regulates Transferrin Receptor 1 Transport and Iron Homeostasis

The study investigated the role of folliculin (FLCN) in regulating transferrin receptor 1 (TfR1) transport and iron homeostasis using human kidney-derived HEK293 cells and a Drosophila model. FLCN promoted the binding of Rab11A with TfR1, essential for iron uptake. Loss of FLCN disrupted this interaction, delaying TfR1 recycling and causing iron deficiency, which activated hypoxia-inducible factor (HIF) activity. Iron supplementation reversed these effects. In Drosophila, an iron-rich diet rescued the phenotype of BHD mutant larvae. These findings highlighted FLCN's conserved function in iron metabolism and provided insights into Birt-Hogg-Dubé (BHD) syndrome mechanisms.