Editing of mRNA controls the ability of the GluA2 subunit to regulate Ca2+-permeability of AMPA receptors. RNA editing is a post-transcriptional modification (Gln; Q to Arg; R) in the GluA2 mRNA, and the AMPA receptor is Ca2+-impermeable if it contains the edited GluA2(R) subunit. Conversely, the receptor is Ca2+-permeable if it lacks GluA2 or if it contains the unedited GluA2(Q) subunit. Interestingly, spinal MNs in human ALS patients display less GluR2 Q/R site editing (Kawahara et al., 2004; Aizawa et al., 2010). GluR2 pre-mRNA is edited by the enzyme adenosine deaminase isoform 2 (ADAR2) (Kortenbruck et al., 2001) and reduced ADAR2 activity correlates with TDP-43 pathology in human MNs (Aizawa et al., 2010). Furthermore, when ADAR2 is conditionally knocked-down in MNs in mice, a decline in motor function and selective loss of MNs in the spinal cord and cranial motor nerve nuclei was observed (Hideyama et al., 2012). In contrast, MNs in the oculomotor nucleus were retained, despite a significant decrease in GluR2 Q/R site editing (Hideyama et al., 2010). Notably, cytoplasmic mislocalization of TDP-43 was present in the ADAR2-depleted MNs (Yamashita et al., 2012) and TDP-43 was also localized at the synapse, further highlighting a link between ADAR2, GluR2 and TDP-43 (Wang et al., 2008; Feiguin et al., 2009; Polymenidou et al., 2011; Gulino et al., 2015).