While the former two mechanisms imply toxic gain‐of‐functions, which has been established in several studies (Almeida et al, 2013; Donnelly et al, 2013; Haeusler et al, 2014; Mizielinska et al, 2014; Zhang et al, 2016; Conlon et al, 2018; Khosravi et al, 2020), the molecular mechanism of how C9orf72 loss‐of‐function contributes to ALS/FTD pathology remains unclear. This evidence concerns the gene C9orf72 and amyotrophic lateral sclerosis.