Function and dysfunction of leucine-rich repeat kinase 2 (LRRK2): Parkinson's disease and beyond.

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson's disease (PD). As such, functions and dysfunctions of LRRK2 in PD have been the subject of extensive investigation. In addition to PD, increasing lines of evidence suggest that LRRK2 is associated with a wide range of diseases. Genome-wide association studies have implicated LRRK2 in Crohn's disease (CD) and leprosy, and carriers with pathogenic mutations of LRRK2 show increased risk to develop particular types of cancer. LRRK2 mutations are rarely found in Alzheimer's disease (AD), but LRRK2 might play a part in tauopathies. How LRRK2 is associated with the pathogenesis of apparently unrelated diseases remains enigmatic, but it might be related to as yet unknown, but perhaps diverse functions of LRRK2. Here, we review current knowledge on the link between LRRK2 and several diseases, including PD, AD, CD, leprosy, and cancer, and discuss the possibility of targeting LRRK2 in such diseases.