One of the main pathological characteristics of ALS is the presence of insoluble protein inclusions in the soma of MNs. TAR DNA binding protein-43 (TDP-43) is the major component of these inclusions (Arai et al., 2006; Neumann et al., 2006) in almost all (∼97%) ALS patients and ∼50% FTD patients (Arai et al., 2006; Neumann et al., 2006; Mackenzie et al., 2007; Scotter et al., 2015; Le et al., 2016). Loss of TDP-43 from the nucleus is evident in MNs from ALS/FTD patient tissues, concomitant with the formation of TDP-43 inclusions in the cytoplasm of both MNs and glia. Neuropathological studies have also revealed that the clinical course of ALS reflects the presence of TDP-43 pathology, from its deposition at an initial site of onset, to its spread to contiguous regions of the CNS (Brettschneider et al., 2013). Mutations in TDP-43 are also present in 5% of familial forms of ALS (Sreedharan et al., 2008). In the genetic types of ALS, it remains unclear why MNs are specifically affected when the mutant proteins are ubiquitously expressed. Males are affected more by ALS than females, and ethnic populations show differences in the incidence rates of ALS, further highlighting the contribution of genetics to ALS.