In ALS and frontotemporal dementia (FTD), AFF2/FMR2 regulates the expression of the C9orf72 allele containing G-rich sequences, and knockdown of AFF2/FMR2 decreases the expression of the mutant allele, resulting in the rescue of axonal degeneration and TDP-43 pathology. Here, AFF2 is linked to amyotrophic lateral sclerosis.