HSP-associated REEP1 mutations are predominantly truncating mutations that have been proposed to act by a haploinsufficiency loss-of-function mechanism (Züchner et al., 2006; Beetz et al., 2008; Schlang et al., 2008; Goizet et al., 2011; Richard et al., 2017). Here, REEP1 is linked to hereditary spastic paraplegia.