The biology and pathology of the familial Parkinson's disease protein LRRK2

Parkinson's disease (PD) is typically a sporadic illness, but the past decade has witnessed the identification of mutations responsible for multiple familial forms of the disease. The proposed functions of some of these genes (e.g., E3 ubiquitin ligase, redox-dependent chaperone) have led to the hypothesis that dysfunction of protein quality control pathways contributes to PD neurodegeneration. However, the key signaling events that act downstream of misfolded proteins to cause cell death remain poorly defined. The discovery of the familial PD kinase leucine-rich repeat kinase 2 (LRRK2) holds great promise for the elucidation of signaling events relevant to PD neurodegeneration. This review will summarize current knowledge of the clinical and cell biological features of LRRK2, the most common inherited cause of Parkinsonism.