Here, we identify bi-allelic loss-of-function of the autocrine motility factor receptor (AMFR, alias GP78), encoding a RING-H2 finger E3 ubiquitin ligase anchored at the endoplasmic reticulum (ER) membrane [9], as a new cause of HSP by altering lipid metabolism. The gene discussed is AMFR; the disease is hereditary spastic paraplegia.