In conclusion, the identification of ALS-associated genetic defects in SOD1, FUS, TDP-43, C9ORF72, TBK1, and OPTN, and the abnormalities in protein homeostasis and autophagosomes associated with these defects support an important role for dysregulated autophagy in ALS pathogenesis. Here, C9orf72 is linked to amyotrophic lateral sclerosis.