The AAA protein family members share an ATPase domain and have roles in various cellular processes including intracellular motility, membrane trafficking, proteolysis, protein folding and organelle biogenesis. Spastin, a member of the AAA protein family, is a 616 amino acid protein and is involved in the function or assembly of nuclear protein complexes. The Spastin protein is expressed ubiquitously and localizes to the nucleus and the cytoplasm, where it may also be involved in microtubule dynamics. Mutations in the Spastin gene (SPAST, SPG4) cause the most common form of spastic paraplegia 4, an autosomal dominant form of hereditary spastic paraplegia (HSP). HSPs comprise a group of inherited neurological disorders characterized by spastic lower extremity weakness due to a length-dependent, retrograde axonopathy of corticospinal motor neurons. SPAST-specific mutations account for approximately 40% of all autosomal dominant HSPs.
