Furthermore, conditional knock-out of TARDBP (Wu et al., 2012) or expression of disease associated mutant TDP-43 at close to endogenous levels [which caused neither loss of nuclear localization of cytoplasmic aggregation (Arnold et al., 2013; Gordon et al., 2019)] resulted in ALS-like phenotypes in mice. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.