The autophagic-lysosomal pathway can be disrupted by ALS-linked mutants of the core components or the modifier factors that regulate autophagic induction (C9ORF72, TBK1), autophagosome formation and maturation (OPTN, SQSTM1, TBK1, UBQLN2, VCP, VAPB), and autolysosome formation (C9ORF72, VCP, CHMP2B, ALS2) [109]. Here, C9orf72 is linked to amyotrophic lateral sclerosis.