VPS53 (Vacuolar Protein Sorting 53 Homolog) is a critical component of the HOPS (Homotypic fusion and Vacuolar Protein Sorting) complex, which mediates lysosomal trafficking and autophagy in eukaryotic cells. The HOPS complex facilitates the fusion of late endosomes with lysosomes, an essential step in the degradative pathway that maintains cellular homeostasis and clears aggregated proteins and damaged organelles. VPS53 is encoded by the VPS53 gene located on chromosome 17p13.1 and is evolutionarily conserved from yeast to humans. In the brain, VPS53 is expressed in neurons and glial cells, with high expression in the cerebral cortex, hippocampus, and cerebellum—regions vulnerable to neurodegeneration. Mutations in VPS53 cause autosomal recessive hereditary spastic paraplegia (HSP) with neurodevelopmental regression, highlighting its critical role in neuronal function. Dysfunction of the HOPS complex and impaired lysosomal trafficking contribute to the accumulation of autophagic debris, a hallmark of Alzheimer's disease, Parkinson's disease, and other neurodegenerative disorders.
VPS53 (Vacuolar Protein Sorting 53 Homolog) is a component of the HOPS (Homotypic fusion and Vacuolar Protein Sorting) complex, which plays a critical role in lysosomal trafficking and autophagy. The HOPS complex facilitates the fusion of late endosomes with lysosomes, a crucial step in the degradative pathway that maintains cellular homeostasis. VPS53 is essential for proper endosomal-lysosomal function, and mutations in this gene have been linked to hereditary spastic paraplegia (HSP), a group of genetic disorders characterized by progressive lower limb spasticity and weakness. The dysfunction of VPS53 and the HOPS complex can lead to impaired autophagic degradation, which is a hallmark of many neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and Huntington's disease.
VPS53 is ubiquitously expressed throughout the body, with high expression in neuronal tissues, particularly in the cerebral cortex, hippocampus, and cerebellum. In the brain, VPS53 is expressed in both neurons and glial cells, with particularly high levels in regions vulnerable to neurodegeneration.