ALS2 and neurodegenerative disease: Although alsin can function as a GEF for both Rab5 and Rac1, alsin colocalizes with Rac1 in the growth cones of neurons and regulates Rac1 signaling and neurite outgrowth through its intrinsic GEF activity, thus suggesting a link between Rac1 disruption and neurodegenerative disease (Topp et al., 2004; Kanekura et al., 2005; Tudor et al., 2005).