Indeed, mutations in genes encoding all subunits of AP-4 (ε1; AP4E1, β1; AP4B1, μ1; AP4M1 and σ1; AP4S1) have been identified as leading to a complex form of hereditary spastic paraplegia (HSP) termed AP-4 deficiency syndrome (henceforth AP-4 deficiency) [5,6]. Here, AP4S1 is linked to hereditary spastic paraplegia.