TARDBP and proteostasis deficiencies: TDP-43 proteinopathies are usually characterized by cytoplasmic accumulation of misfolded and heavily modified TDP-43, accompanied by nuclear clearance.8–10 The origin of these aggregates is debatable, but stress granule and dynamics are thought to play a role.11–13 Even though the exact mechanisms remain largely unknown, pathological TDP-43 is thought to exert a plethora of deleterious effects ranging from nuclear transport inhibition by sequestering transport factors,14 to impaired autophagy and mitochondrial dysfunction,15 among others.