When we recapitulated the same assay between Tdp-43 and Lig4 in spinal cord samples of both mutant and sham mice, puncta were observed in the cytosol of ALS-affected neurons surrounding the nuclear periphery, unlike the sham mice (Supplementary Fig. S4), suggesting sequestering of Xrcc4 and DNA Lig4 with mislocalized Tdp-43 aggregates in the cytosol. This evidence concerns the gene LIG4 and amyotrophic lateral sclerosis.