Mutations in the ζ-subunit of AP 5 complex (SPG48), encoded by the AP5Z1 gene, as well as in the associated proteins spatacsin (SPG11 or called KIAA1840) and spastizin (SPG15 or called ZFYVE26) lead to an accumulation of aberrant endolysosomes filled with undigested material, and highlight the role of endolysosomal dysfunction in the pathology of HSP and other neurodegenerative disorders [167,168,169]. Here, AP5Z1 is linked to hereditary spastic paraplegia.