We [92] and others 91,153–155,163,164 are proposing RNA mediated gain-of-function toxicity as one contributing mechanism operating to prevent aberrantly bound/sequestered RNA-processing factors from functioning normally in the nucleus, which in turn leads to broad alteration of gene expression in C9ORF72-related ALS. Here, C9orf72 is linked to amyotrophic lateral sclerosis.