TARDBP and proteostasis deficiencies: To investigate whether this dimerization links to pathological conditions in TDP-43 proteinopathy, we generated recombinant proteins for the RRM2 domain (aa 190–265) of human WT TDP-43 and several substitution mutants of E246 and/or D247, which are conserved acidic amino acids among various species (Fig. 1A, a).