A unifying hypothesis for the multitude of genetic causes of HSP may be that implicated mutant proteins may either alter the structure or form of proteins that contain APH domains (e.g., M1-spastin, atlastin-1, REEP1/2) or alter the lipid composition or structure of ER and/or Golgi membranes (e.g., DDHD1/2, PNPLA2, CYP7B1, and CYP2U1). The gene discussed is SPAST; the disease is hereditary spastic paraplegia.