Of note the cytotoxicity of overexpressed TDP-43 and that of proteasome inhibition is mediated by phosphorylation of the ubiquitin-binding domain of the autophagy cargo receptor p62 by tank-binding kinase 1 (TBK1) [175], which is mutated in up to 4% of ALS and FTLD cases and up to 10.8% of FTLD-ALS cases [176]. The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.