NPC1 and amyotrophic lateral sclerosis: Thus, because the NPC has been shown to play important roles in DNA repair and the organization of genome architecture [128] while in response to DNA damage chromatin undergoes dramatic genome-wide changes that are at the heart of DDR [129], further scrutiny will be required to apprehend the relationship between nuclear DPR accumulation at specific nuclear structures (i.e. NPC), imbalanced chromatin states and their link to DDR in ALS.