While we do not suspect or propose that the loss of SV2 is the root cause of ALS in these patients, it should be considered as a further contributing factor to the multifactorial abnormal environment created by the presence of the C9orf72 hexanucleotide repeat expansion, associated RNA foci, and the other dipeptide repeat protein variants. The gene discussed is C9orf72; the disease is amyotrophic lateral sclerosis.