Spatacsin (SPG11) (SPG11)

SPG11 encodes spatacsin, a large, evolutionarily conserved cytoplasmic protein highly expressed in the nervous system whose precise biochemical function remains incompletely defined.[5][4] Spatacsin participates in late endosome/lysosome biology, cooperating with SPG15 to recruit the AP-5 adaptor complex to late endosomes/lysosomes, and has been linked to autophagy-lysosomal pathway integrity and vesicle trafficking.[3][4] Human biallelic loss-of-function variants in SPG11 cause spastic paraplegia type 11, the most frequent complex autosomal recessive HSP, typically featuring progressive spastic paraparesis, cognitive decline, peripheral neuropathy, and a characteristic thin corpus callosum on MRI.[9][4] Transcriptomic analyses in Spg11−/− mouse brain tissues further implicate dysregulation of inflammation, RNA metabolism, neuronal/neurite development, proteostasis pathways, and cell-cycle programs, supporting a role for spatacsin in neurodevelopmental and neurodegenerative processes.[2] Although SPG11 has genetic and mechanistic importance in disease, it is not an established pharmacological target and no drugs currently act directly on spatacsin.[4][5]

Other names

KIAA1840FLJ21439Spastic paraplegia 11 (autosomal recessive)SPATACSINSPTCS_HUMAN