R-loop-mediated DNA damage may contribute to the pathogenesis of different forms of ALS caused by mutations in the superoxide dismutase 1 (SOD1), open reading frame 72 at chromosome 9 (C9ORF72), fused in sarcoma (FUS), and transactivation response DNA binding protein, 43kDa (TDP-43) genes. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.