C9 and amyotrophic lateral sclerosis: Loss of C9orf72 function has been linked to disruption of autophagy and lysosome function, though neurodegeneration is not observed in C9orf72 knockout mice (Liu et al., 2016; Shi et al., 2018; Webster et al., 2016), suggesting that C9-ALS/FTD is primarily caused by toxicity of the HRE.