Because C9ORF72 has documented roles in endocytosis with its RNAi-mediated KD impacting on lysosomal degradation and autophagy (Farg et al, 2014), its LOF in ALS could stress cells through perturbed trafficking, protein turnover, and ROS accumulation (Ferraiuolo et al, 2011; Sasaki, 2011; Otomo et al, 2012), eventually leading to DSB accumulation as neurons are dying. The gene discussed is C9orf72; the disease is amyotrophic lateral sclerosis.