The stress-dependent recruitment of TDP-43 to NBs is diminished by the ALS-causing D169G mutation within RRM1, while the formation of TDP-43-containing SGs is conversely significantly enhanced in the cytoplasm, raising the possibility that assembly of TDP-43-containing NBs works as the first line of defense against stress to prevent excessive recruitment and accumulation of TDP-43 in cytoplasmic SGs [45]. Here, RRM1 is linked to amyotrophic lateral sclerosis.