Determining protein constituents associated with detergent-insoluble inclusions that are specific to TDP-43 proteinopathies compared with other proteinopathies, for example those seen in Parkinson’s disease (PD) or Alzheimer’s disease (AD), could increase understanding of the wider consequences of TDP-43 aggregation on ALS pathogenesis, identify druggable pathways, and aid the development of specific biomarkers to stratify patients by TDP-43 molecular diagnosis. This evidence concerns the gene TARDBP and proteostasis deficiencies.