Almost all ALS- and FTD-linked TDP-43 mutations lie in the PrLD, and several of these mutations can promote deleterious TDP-43 misfolding and enhance proteotoxicity in diverse model systems (Barmada et al., 2010; Guo et al., 2011; Johnson et al., 2009; Kabashi et al., 2010; Li et al., 2010; Lim et al., 2016; Ling et al., 2013; Ritson et al., 2010; Sreedharan et al., 2008; Zhang et al., 2009). Here, TARDBP is linked to amyotrophic lateral sclerosis.