This is also the case with REEP1, in which frameshift mutations or missense mutations that abolish ER targeting and affect the capacity of the protein to bind ATL1 (Falk et al. 2002; Beetz et al. 2012) lead to HSP (Züchner et al. 2006; Beetz et al. 2008; Hewamadduma et al. 2009; Goizet et al. 2011), whereas in-frame deletions do not impact the capacity of the protein to bind ATL1 and lead to hereditary motor neuropathy type V (Beetz et al. 2012). This evidence concerns the gene ATL1 and hereditary spastic paraplegia.