Deposition of filamentous structures of α-synuclein(α-syn) in the neuronal cytoplasm is a common pathological feature of many neurological diseases, such as Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Lysosome is one of the main clearance ways for α-syn degradation. The α-syn accumulation has been found in the lysosome enzyme Cathepsin D (CD) deficient mice in our previous work. However, little is known about how cells handle protein aggregates. To study the process of α-syn accumulation, the bands in the α-syn Western blot were analyzed in the soluble and insoluble homogenate of the wide type and CD knock out mice. Obvious changes were not found in the monomer α-syn, however, they were found in other bands, especially between 25~37 kD. These results suggest that lysosomal functions are important to the equilibrium of α-syn metabolism, especially to the oligomer. It is speculated that natural α-syn may exist in the form of monomer, as well as oligomer. The dysfuction of lysosomal will lead to the imbalance between monomer and oligomer of α-syn untill the α-syn form accumulation.