Although cryptic exon inclusion likely involves multiple factors beyond just the loss of one repressor, the fact that TDP-43 functions as a splicing repressor of cryptic exons and that this function is impaired in the brains of ALS and FTD patients leads to the hypothesis that the nuclear clearance of TDP-43 has a crucial role in suppressing cryptic exons. Here, TARDBP is linked to amyotrophic lateral sclerosis.