In FUS-ALS motor neuron loss is primarily driven by a gain-of-function mechanism (Scekic-Zahirovic et al., 2016, 2017; Sharma et al., 2016; Shiihashi et al., 2016), and the focus has been on cytoplasmic gain-of-function because mutant FUS is mislocalized and the level of mislocalization has been linked to disease severity (Bosco et al., 2010; Dormann et al., 2010; Higelin et al., 2016). Here, FUS is linked to amyotrophic lateral sclerosis.