LRRK2 function in pulmonary homeostasis and fibrosis

Emerging data implies a significant risk of pulmonary fibrotic changes secondary to LRRK2 inhibition in rodents and primates. LRRK2 global loss-of-function mice develop more severe pulmonary fibrosis following bleomycin-induced lung injury. We hypothesize that LRRK2 kinase function is critical for pulmonary homeostasis preventing development of PF. Here, we will define the mechanism by which LRRK2 functions in lung biology, thereby characterizing a targetable pathway in pulmonary fibrosis and elucidating risks associated with LRRK2-targeted therapies in active clinical development for PD.