C9orf72 and amyotrophic lateral sclerosis: Several studies have also shown that loss of function of C9orf72 can affect endosomal trafficking (O’Rourke et al., 2016; Farg et al., 2017; Shi et al., 2018), which could contribute to causing FTD and ALS in concert with gain-of-function mechanisms (Balendra and Isaacs, 2018).