In the case of C9orf72-ALS/FTD where TDP-43 is the major pathology, the arginine rich DPRs bind to importin-α and β, reducing their solubility and lead to their precipitation and condensation; this results in defective nuclear import of TDP-43, and thus likely contributes to the dominant TDP-43 pathology (Hutten et al., 2020). Here, C9orf72 is linked to frontotemporal dementia.