Spatacsin vesicle trafficking associated (SPG11) (SPG11)

SPG11 (Spatacsin vesicle trafficking associated) is a gene that encodes the protein spatacsin, a critical regulator of intracellular trafficking and lysosomal dynamics. Spatacsin functions as a subunit of the adaptor protein complex 5 (AP-5) and is essential for autophagic lysosome reformation (ALR), a recycling process that regenerates functional lysosomes from autolysosomes. Loss-of-function mutations in the SPG11 gene are the most frequent cause of autosomal recessive hereditary spastic paraplegia with a thin corpus callosum (ARHSP-TCC), leading to progressive motor impairment, cognitive decline, and neurodegeneration. At the cellular level, SPG11 deficiency results in the depletion of the lysosomal pool and the accumulation of autolysosomes, which impairs axonal transport and neuronal survival, particularly in long-range corticospinal neurons. While there are currently no FDA-approved disease-modifying treatments, SPG11 RNA and the gene itself are primary targets for emerging genetic therapies. Research is focused on utilizing antisense oligonucleotides (ASOs) to modulate SPG11 RNA splicing or employing gene replacement strategies to restore spatacsin function and halt the progression of neurodegenerative symptoms.

Other names

SpatacsinKIAA1840Hereditary spastic paraplegia 11 proteinSPG11 RNASPG11 mRNA

Restoration of spatacsin protein levels through gene replacement therapy or modulation of SPG11 RNA using antisense oligonucleotides (ASOs) to correct splicing or enhance translation.