New research from Xia et al. (2015) has identified a role for FLCN in the cytosolic translocation and aggregation of the RNA/DNA binding protein TDP-43. Although TDP-43 is usually shuttled between the nucleus and the cytosol, enhanced translocation out of the nucleus and cytosol aggregation is associated with neuronal loss in ALS and FLTD. Xia et al. report that overexpression of FLCN, which directly interacts with TDP-43, results in enhanced TDP-43 translocation into the cytosol and the formation of stress granules. In contrast a depletion of FLCN increased nuclear deposition and dissociates TDP-43 from other stress granule proteins in the cytosol. Further research is required to clarify the role of FLCN in TDP-43 pathologies.