With a potent, fast and selective LRRK2 degrader in hand, we next established XL01126 cellular functionality in bioassays that report on LRRK2 activity. Mitochondrial dysfunction is one of the pathophysiological hallmarks of PD and can be rescued by mitophagy, a quality control mechanism whereby damaged or unnecessary mitochondria are delivered to lysosomes for degradation through membrane trafficking . It has been shown that increasing mitophagy with inducer agents has the potential as a PD therapy . Previous studies have shown that LRRK2 kinase activity impairs basal mitophagy and that LRRK2 knockout or pharmacological inhibition of LRRK2 with kinase inhibitors was able to rescue the mitophagy level . Utilizing XL01126 as a chemical degrader tool and using cis-XL01126 as a non-degrader, kinase inhibitor control, we found that both XL01126 and cis-XL01126 induced mitophagy level dose-dependently (Figure ) in mito-QC MEFs, a mCherry-GFP-mitochondria reporter cell model developed previously . Although XL01126 and cis-XL01126 act on LRRK2 through different mechanisms, they shared similar potency in inducing mitophagy at 10-100 nM, indicating that mitophagy level is indeed LRRK2 kinasedependent, and that other domains or motifs of LRRK2 are not involved in regulating mitophagy.