Alpha-synuclein is a normal protein found in the brain. It is predominantly a presynaptic neuronal protein of unknown function, but can also be found in glial cells.

Normally an unstructured soluble protein, alpha-synuclein can aggregate to form insoluble fibrils in pathological conditions characterized by Lewy bodies, such as Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Alpha-synuclein is the primary structural component of Lewy body fibrils.

In rare cases of familial forms of Parkinson's disease there is a mutation in the gene coding for alpha synuclein. Two point mutations have been identified thus far: A53T and A30P. In addition, triplication of the gene appears to be the cause of Parkinson's disease in another lineage.

Antibodies against alpha-synuclein have replaced antibodies against ubiquitin as the gold standard for immunostaining of Lewy bodies.