We thus chose two paradigmatic FTD-causing MAPT mutations with either increased (V337M) or decreased (N297K) microtubule binding and hypothesized that (I) MAPT mutations affect axonal trafficking of mitochondria and lysosomes and (II) that different TAU binding affinities differentially affect axonal trafficking of organelles in human patient-derived neurons. The gene discussed is MAPT; the disease is frontotemporal dementia.