Complex hereditary spastic paraplegias, such as spastic paraplegia type 15 (SPG15) is a very rare neurodegenerative disease which onset typically starts in childhood or adolescence. It is knowing to cause paralysis in the lower and upper limbs with neurological impairment, which may include dysarthria, dysphagia and extrapyramidal signs like dystonia (continuous spasms and muscle contractions), akathisia (motor restlessness), parkinsonism (characteristic symptoms such as rigidity), bradykinesia (slowness of movement), tremor, and tardive dyskinesia (irregular, jerky movements).

Onset of symptoms in SPG15 typically occurs in childhood or adolescence and the first symptom is often either leg stiffness or intellectual disability. Neurological symptoms may include learning difficulties and intellectual disability, structural brain malformations (e.g., thinning of the tissue that connects the left and right halves of the brain, the corpus callosum), loss of nerve cells in different parts of the brain, involuntary movements, and dementia. These issues may be progressive. Additional symptoms may include numbness, tingling or pain in the arms and legs, problems with muscle movements and reflexes, and issues with bladder control. Some individuals with SPG15 also have problems with the retina in the eye, which can cause visual impairment. The severity of each of these symptoms is variable in affected individuals.

SPG15 is caused by mutations in the ZFYVE26 gene. It is a progressive autosomal recessive disease, which means that both parents have passed on a mutation to defect the gene. ZFYVE26 encodes the FYVE domain-containing protein ZFYVE26/SPASTIZIN, which is associated with the adaptor protein 5 (AP5) complex.