Notably, substrates and regulators of the Ran GTPase cycle were found to be powerful genetic modifiers of proteotoxicity or proteostasis of ALS substrates (Cho et al., 2015b; Cho et al., 2014; Zhang et al., 2015; Freibaum et al., 2015; Jovičić et al., 2015; Boeynaems et al., 2016). Here, RAN is linked to amyotrophic lateral sclerosis.