Many disease-associated mutations occur in proteins that function in protein turnover such as the UPS and autophagy, including C9orf72, charged multivesicular body protein 2b, optineurin, sequestrome 1, serine/threonine protein kinase TBK1, ubiquilin 2 and valosin-containing protein (VCP), suggesting broad impairment of protein turnover in neurodegenerative disease (Balendra and Isaacs, 2018; Gao et al., 2017; Taylor et al., 2016). This evidence concerns the gene OPTN and neurodegenerative disease.