Interestingly, although we observed that wild-type (WT) and mislocalized TDP-43 with a mutant nucleus localizing signal (NLS) are comparatively pulled down with poly-ubiquitin in cell culture studies12, TDP-43 in ALS tissues or with cysteine substitution mutants in RRM1 is more heavily ubiquitinated than normally folded species4, 5, 10. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.