LRRK2 in Infection: Friend or Foe?

Abstract In the field of Parkinson’s disease (PD) research, leucine-rich repeat kinase 2 (LRRK2) remains one of the most enigmatic kinases. LRRK2 pathogenic mutations result in increased kinase activity, making LRRK2 an attractive therapeutic target for PD. For over 10 years, the identification of a bona fide substrate and a physiological function for LRRK2 has been elusive, and only recently, Rab GTPases were identified as substrates for LRRK2 kinase activity. Additionally, LRRK2 gene expression data shows that LRRK2 is expressed at low levels in neurons and at high levels in cells of the immune system. These findings shifted research efforts from neuronal toxicity of LRRK2 mutations to the function of LRRK2 in both vesicle trafficking and the immune system, which has resulted in novel insights into the role of LRRK2 during infection and immunity. In this Perspective, we summarize the latest findings highlighting LRRK2 as a central regulator of vesicular trafficking, infection, immunity, and inflammation, speculating how LRRK2 function could influence neuronal pathology in PD.