Notably, alterations in the RNA recognition domain, RRM1 of TDP-43 via oxidation can induce its aggregation and mislocalisation into the cytoplasm [26,27,28] and structure/function analysis has shown that misfolding of the RRM1 domain could underlie TDP-43 misfolding, oligomerisation, accumulation, and ultimately proteinopathy [27,29]. Here, TARDBP is linked to proteostasis deficiencies.