p62 downregulation or overexpression of RNF168 improved DSB repair and decreased levels of DSBs in cells overexpressing C9orf72 mutations, indicating that defective autophagy, induced by p62 accumulation, is a major cause of genome instability in C9orf72-ALS disease models [295]. Here, C9orf72 is linked to amyotrophic lateral sclerosis.