AP4S1 and hereditary spastic paraplegia: Notably, biallelic loss-of-function mutations in each of these four AP-4 subunits lead to clinically overlapping HSP types, including SPG47 (AP4B1), SPG50 (AP4M1), SPG51 (AP4E1), and SPG52 (AP4S1), which could be collectively called “AP-4-associated HSP” or “AP-4 deficiency syndrome” (5–7).