While some ALS mutants in the FUS NLS domain cause ~50% of the protein to mis-localize to the cytoplasm, the FUS Arg521Cys (R521C) mutation causes aggregate formation [36] and a minor nuclear trafficking defect with only ~10% of the protein mis-localized to the cytoplasm [37]. The gene discussed is FUS; the disease is amyotrophic lateral sclerosis.