ALS-causing mutations in the gene encoding Sigma receptor-1, and C9orf72 hexanucleotide expansions (a leading cause of both sporadic and familial forms of ALS in populations with European ancestry) are also associated with ER Ca2+ dyshomeostasis due to combinations of elevated IP3R activity and diminished uptake into stores [282,283]. Here, ITPR1 is linked to amyotrophic lateral sclerosis.