All of the proteins we have shown to co-localize with RNA foci, many of the binding partners identified in our RNA pulldown, and a number of the proteins implicated in genetic variants of ALS including TARDBP, EWSR1, FUS, HNRNPA1 and HNRNPA2B1, have been localized to nuclear speckles (Zhou et al., 2000; Saitoh et al., 2004; Casafont et al., 2009). This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.