Notably, iPSC-derived neurons from C9orf72-ALS cases exhibited downregulation of both LSM12 and EPAC1 at both protein and mRNA levels and exhibited mislocalization of both Ran-GTPase and TDP-43, which could be rescued by LSM12 or EPAC1 overexpression (Lee et al., 2020b). This evidence concerns the gene RAN and amyotrophic lateral sclerosis.