Therefore, considering that (i) CTIF is enriched in the inclusion bodies seen in neurodegenerative diseases25, (ii) UPF1 associates with the CED complex (Fig. 5), and (iii) UPF1 is required for efficient CED-mediated targeting of misfolded polypeptides toward the aggresome (Figs. 2–4), our data provide molecular insights into a cytoprotective function of UPF1 in neurodegenerative diseases linked with accumulation of misfolded polypeptides. Here, CTIF is linked to neurodegenerative disease.