SMCR8 and amyotrophic lateral sclerosis: TBK1 regulates autophagy through phosphorylation of Optineurin3 and the C9ORF72/SMCR8 complex.4 Of note, mutations in both Optineurin5 and the C9ORF72/SMCR8 complex6,7 cause monogenic forms of amyotrophic lateral sclerosis and frontotemporal dementia.