Multiple factors have been hypothesized over the years to be contributory and or causative for Parkinson's disease (PD). Hereditary factors, although originally discounted, have recently emerged in the focus of PD research. The study of a large Italian family with PD using a genome scan approach led to the mapping of a PD susceptibility gene to the 4q21-q23 genomic region, where the gene for alpha-synuclein was previously mapped. Mutation analysis of the alpha-synuclein in four unrelated families with PD revealed a missense mutation segregating with the illness. Alpha-synuclein is an abundant presynaptic protein of the human brain of unknown function. It is conceivable that the mutation identified in the PD families may result in self-aggregation and or decreased degradation of the protein, leading to the development of intracytoplasmic inclusion bodies and eventually to neuronal cell death. Moreover, the discovery of a mutation in the synuclein gene may offer us new insights into the understanding of the pathways that lead to neuronal degeneration.