C9orf72 and amyotrophic lateral sclerosis: Considering that the GGGGCC repeat expansion in a noncoding region of the C9orf72 gene is the most common genetic cause of ALS/FTD and directly causes disrupted energy metabolism, especially OXPHOS, in patient-derived cells39,64, we analyzed eSG formation under severe energy deficiency in C9-ALS patients’ iPSC-derived cortical organoids (COs) that mimic human brain tissues (Fig. 6a).