ALS2 and amyotrophic lateral sclerosis: Several familial ALS genes (ALS2 [Hadano et al., 2001; Kunita et al., 2004], FIG4 [Chow et al., 2009], and CHMP2B [Skibinski et al., 2005; Parkinson et al., 2006]) have clear endolysosomal functions, with ALS2 being a Rab5 guanine exchange factor (GEF), FIG4 being involved in PI(3)P synthesis (critical for early endosome and autophagosome biogenesis), and CHMP2B being an ESCRT-III complex factor.