ALS2 and Juvenile onset: 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).