Interestingly loss-of-function mutations in optineurin, p62 and TBK1 have been shown to cause ALS, and the C9orf72 protein regulates autophagy and interacts with SMCR8 which is itself a TBK1 substrate (Webster et al., 2016a, Webster et al., 2016b, Ugolino et al., 2016, Yang et al., 2016). This evidence concerns the gene OPTN and amyotrophic lateral sclerosis.