TARDBP and amyotrophic lateral sclerosis: In terms of C9orf72-ALS, it is possible that nuclear import receptor chaperone activity could buffer R-DPR toxicity until R-DPR concentration exceeds a threshold or nuclear import receptor function is compromised by another C9orf72 pathomechanism, whereby import and chaperone functions of nuclear import receptors are overwhelmed, eventually leading to TDP-43 mislocalization.