DISC1 and neurodegenerative disease: Although misfolded TDP-43 has well-delineated toxicity on its own, including the initiation of ER stress and mitochondrial dysfunction (54, 55), a recently recognized toxic activity of misfolded or aggregated TDP-43 is to trigger the misfolding and dysfunction of other proteins, including nuclear pore proteins and karyopherins (56), proteins involved in mRNA translation (RACK1, DISC1) (57, 58), and proteins implicated in other neurodegenerative diseases (tau, alpha synuclein) (59, 60).