DPRs such as poly-GR and poly-PR, produced via repeat-associated non-AUG (RAN) translation, disrupt the RanGTP gradient required for NCT, thereby impairing nuclear import and exacerbating the cytoplasmic mislocalization of TDP-43—an established pathological hallmark of ALS (Allegretti et al., 2020; Khosravi et al., 2017). Here, TARDBP is linked to amyotrophic lateral sclerosis.