Though the exact pathological role of TDP-43 in ALS-FTD and other TDP-43 proteinopathies remains incompletely understood, it’s believed that its depletion from the nucleus and/or its abnormal deposition into cytoplasmic inclusions may give rise to gain and/or loss of functions that drive its toxicity1,8–10, a hypothesis supported by the discovery that its mutation is also associated with disease11–14. This evidence concerns the gene TARDBP and proteostasis deficiencies.