Importantly, the fALS-associated OPTN mutations in the UBAN domain, such as E478G and Q398X, abolished the inhibitory effects of OPTN on canonical NF-κB activation, and M1-ubiquitin is colocalized with TDP-43 inclusions in neurons from OPTN-associated ALS patients (Maruyama et al., 2010; Nakazawa et al., 2016). Here, TARDBP is linked to amyotrophic lateral sclerosis.