Alterations to this pathway are directly implicated in ALS, ALS-FTD, FTD and/or Multisystem Proteinopathy pathogenesis through mutations to OPTN, SQST1, VCP and the recently discovered TBK1 (Renton et al., 2014; Freischmidt et al., 2015). Here, TBK1 is linked to amyotrophic lateral sclerosis.