Taken together, these results support a model in TDP-43 proteinopathy, including Perry disease (Figure 7A): dysregulation of DCTN1-TDP-43 interactions disrupts dynein-dependent retrograde transport of TDP-43 and causes cytoplasmic mislocalization and aggregation of TDP-43, with concurrent aggregation of DCTN1. This evidence concerns the gene DCTN1 and proteostasis deficiencies.