Autosomal recessive and HSP-associated mutations in ERLIN1, ERLIN2, and RNF170 as well as autosomal dominant missense mutations in ERLIN2—in contrast to the RNF170 missense mutation reported to cause ADSA9—are thus all predicted to lead to an increase of basal IP3R levels and impairment of IP3R degradation. Here, ITPR1 is linked to hereditary spastic paraplegia.