Importantly, the uncovering of two ALS loci, Sod1 and TDP43, mTOR pathway genes such as Rheb and S6k, and genes enriched in the UPS as modulators of VAP(P58S) aggregation dynamics, led us to develop an in vivo model to validate these genes and to understand mechanisms underlying these interactions in Drosophila. Here, RHEB is linked to amyotrophic lateral sclerosis.