Our model would also potentially explain other genetic forms of HSP that are caused by mutations in genes that would be predicted to impact axonal trafficking, including SPG10, which encodes a kinesin heavy chain isoform involved in anterograde transport in axons; SPG4, which encodes Spastin, a protein involved in catalyzing microtubule severing; and SPG20, which encodes Spartin, a protein involved in endosomal trafficking and microtubule dynamics37–39. Here, SPART is linked to hereditary spastic paraplegia.