Interestingly, mutations in alsin (ALS2), which cause juvenile-onset ALS, disturb its Rab5-GEF activity and consequently disrupt Rab5-dependent endosome trafficking and AMPA receptor trafficking (Hadano et al., 2006, Lai et al., 2006, Devon et al., 2006, Lai et al., 2009). Here, ALS2 is linked to amyotrophic lateral sclerosis.