These observations and the phenotypic variability of same genotypes suggest the consideration of a decisive contribution of additional factors in the pathogenesis of ALS2 disorders, mainly of genes coding for molecules interacting with alsin along its multiple functions, particularly in the endolysosomal pathway [21], that may display functional variations due even to subtle changes, no necessarily to pathogenic variants, attributable to diversity of the genomic dotation of ALS2 mutation carriers including of siblings. Here, ALS2 is linked to amyotrophic lateral sclerosis type 2, juvenile.