The D169G mutation was identified in one sporadic ALS case (Kabashi et al., 2008) and shown not to have any impact on RNA binding in in vitro studies despite its location at the RRM1 domain (Fig. 5A; Austin et al., 2014; Kuo et al., 2014), nor functional disruption to full length TDP-43 (McDonald et al., 2011; Vanden Broeck et al., 2015). This evidence concerns the gene RRM1 and amyotrophic lateral sclerosis.