C9orf72 and amyotrophic lateral sclerosis: It remains to be determined whether loss of C9orf72 protein function and toxic gain of function by RNA foci formation and DPR inclusion act in a concerted manner to manifest neurodegeneration in ALS and patient-derived cell models may be a more appropriate model for addressing these questions as they carry the HRE in a natural genetic context and the protein is expressed at physiological levels.