 Amiatrophic lateral sclerosis, ALS, is a lethal neurodegenerative multi-system disease. In 90 to 95 percent of cases, ALS is sporadic, but close to 10 percent of ALS is familial with inherited gene mutations from family members. This opinion piece proposes that ALS genes are associated with the piezo-2 channelopathy mechanism both downstream and upstream. This article was authored by Balash Songkoti.