C9orf72 haploinsufficiency also negatively affects vesicle trafficking and inhibits the initiation of autophagy.506 Inhibition of autophagy impedes the clearance of misfolded and aggregated proteins, such as TDP-43 and FUS aggregates in ALS, thereby exacerbating cellular damage. This evidence concerns the gene C9orf72 and amyotrophic lateral sclerosis.