The disruption of ER–endosomal interactions also affects endosomal sorting and leads to lysosomal defects (Section 2.2.6 and 3.1.2), and this is frequently linked to diseases such as HSP and ALS (Table 1), where it can be caused by mutations in spastin, strumpelin, REEP1 [177], and VAPB, as described elsewhere in this special issue [291]. Here, SPAST is linked to hereditary spastic paraplegia.