The observations of ER Ca2+ homeostasis disruption and HSP development as a result of altered TREX1 function are supported by recent studies on the pathogenesis of HSP, which showed that mutations in ER-related genes and their associated Ca2+ homeostasis pathways are extensively involved in the progression of HSP [16, 18, 35, 36]. Here, TREX1 is linked to hereditary spastic paraplegia.