Although the precise pathogenic mechanisms involving DDHD2 are not known, mutations in genes involved in common intracellular signaling pathways involving HSP, Parkinson’s disease, amyotrophic lateral sclerosis and Alzheimer’s disease have recently been reported [5, 14] and gene knockouts in drosophila suggest a role for DDHD2 in synaptic organization and transmission [11]. Here, DDHD2 is linked to hereditary spastic paraplegia.