The cytoplasmic mislocalization of TDP-43 represents a distinct key pathological feature of degenerating neurons in 50-70% patients with frontotemporal dementia (FTD). Our most recent study has revealed that TDP-43 accumulates in mitochondria in FTD patients and experimental models. And, importantly, the suppression of TDP-43 mitochondrial localization is sufficient to abolish the TDP-43 toxicity on mitochondria and neurons. In this study, we will use reprogrammed human neurons derived from patients bearing FTD-associated TDP-43 mutations, TDP-43 transgenic mice, a novel synthesized peptide inhibiting TDP-43 mitochondrial localization and a newly identified FDA-approved drug with significant inhibitory effects on mitochondrial TDP-43 in human neurons to test whether the suppression of TDP-43 mitochondrial accumulation could be a promising novel therapeutic approach for FTD patients. As the drug(s) to be identified has a history of safe use in clinical trials, repurposing of them may lead to novel therapeutic approaches for FTD.