[1] The disease is characterised by progressive spasticity that starts within the lower extremities and spreads to the upper body and limbs.

[5] At the molecular level, SPG15 is caused by loss of function mutations in the ZFYVE26 gene, encoding the protein spastizin.

The exact mechanism of action of cellular locations of spastizin have not been totally elucidated yet, but it is generally accepted that it interacts with the protein spatacsin and a complex containing AP5Z1, that when mutated are responsible for other forms of HSP, SPG11 and SPG48.

[6] Mouse models with Zfyve26 mutations show abnormal accumulation of vesicle-like structures, which leads to degeneration of the nerves and the development of the typical signs of the disease.

Research is focussed on the fundamental understanding of the SPG15 protein in maintaining normal cell function and how this related degeneration of nerve cells[10][11] SPG15 is classified as a rare disease with a prevalence of around ~75 individuals worldwide ranging from Europe, North and South America, the Middle East, East Asia.