These findings suggest that CHCHD10S59L-induced ALS-FTD shares a disease-causing mechanism through mitochondrial translocation of TDP-43 with other subtypes of ALS-FTD and that modulating mitochondrial function by targeting PINK1-mediated pathways may provide a therapeutic strategy for CHCHD10-mediated disease. Here, PINK1 is linked to frontotemporal dementia.