While pathogenic variants in other members of the AP5 complex, i.e., ZFYVE26 (causing SPG15 HSP) and AP5Z1 (causing SPG48 HSP), have recently been associated with mitochondriopathy (Denton et al., 2018), our data provide first human evidence that mitochondrial morphology and function is also altered in the more frequent SPG11 type of HSP. Here, AP5Z1 is linked to hereditary spastic paraplegia.