Cytoplasmic inclusions of TDP-43 are accompanied with the depletion of TDP-43 in the nucleus of affected neurons of ALS/FTD patients, and therefore, two major pathogenic mechanisms have been suggested; a gain of toxic function triggered by TDP-43 aggregation, and loss of the physiological functions of TDP-43 through its mislocalization [19, 20]. Here, TARDBP is linked to frontotemporal dementia.