C9ORF72 HRE-positive ALS causes typical TAR DNA-binding protein 43 (TDP-43) positive pathology but also results in a reduction in C9ORF72 transcript levels, accumulation of repeat RNA in intracellular foci, and inclusions of dipeptide protein aberrantly translated from the hexanucleotide RNA. Here, TARDBP is linked to amyotrophic lateral sclerosis.