The mechanisms whereby VCP, SOD1, or C9orf72 mutations converge into regulation of intron retention of overlapping genes are so far unknown, but the observation from the same authors that astrocytes knocked-out for TDP-43 display a similar pattern of splicing alteration suggests that TDP-43 dysfunction, which is common to the majority of ALS cases, might have a role in the process. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.