Three variants were identified in PPMS patients: KIF5A (associated with spastic paraplegia 10), MLC1 (associated with megalencephalic leukodystrophy with subcortical cysts), and REEP1 (associated with spastic paraplegia 31), and the burden of genetic variants associated with HSP was higher in PPMS patients than controls. Here, KIF5A is linked to primary progressive multiple sclerosis.