We identified that insufficient FXN levels in the hBMVEC BBB model causes changes in cytoskeletal architecture and tight junction protein abundance, coincident with increased barrier permeability. Changes in the integrity of the BBB may be related to patient brain iron accumulation, neuroinflammation, neurodegeneration, and stroke. Furthermore, our findings implicate other barrier cells, e.g., the cardiac microvasculature, as loci of disease pathology in FRDA.