Although HSP is caused by mutations in many genes (Hensiek et al., 2015), mutations in SPAST (also known as SPG4) are by far the most frequent, affecting up to 60% of families with autosomal dominant HSP, and around 10–20% of cases unselected by family history (Hazan et al., 1999; Fonknechten et al., 2000; Sauter et al., 2002; Schule et al., 2016). Here, SPAST is linked to hereditary spastic paraplegia.