Biallelic loss-of-function mutations in the genes encoding the 3 other subunits of the adaptor protein complex 4 (AP-4), namely AP4B1, AP4E1, and AP4S1, also lead to childhood-onset hereditary spastic paraplegia (SPG47, SPG51, and SPG52), establishing a common phenotype, an “AP-4 deficiency syndrome” (1, 2, 4). Here, AP4E1 is linked to hereditary spastic paraplegia.