As one of the most promising disease-modifying targets, LRRK2 lies at the nexus of an emerging signaling network of high relevance for understanding and developing treatments for PD . Although three LRRK2 targeting therapies are already in clinical trials, the exact mechanism by which LRRK2 mutations and its kinase activity contribute to the development of PD is still under investigation. Rab GTPases implicated in vesicular trafficking have been identified as bona fide physiological substrates of LRRK2 , but many components involved in the upstream and downstream wiring of LRRK2 signaling pathways are yet to be discovered, and the question remains as to whether LRRK2 kinase inhibitors will have beneficial disease-modifying effects in PD patients. More indepth LRRK2 target validation is therefore warranted. Induced target protein degradation is a paradigm-shifting drug discovery approach. Heterobifunctional degraders (also known as PROTACs) can induce target protein degradation by recruiting an E3 ubiquitin ligase in proximity to the target protein, resulting in the polyubiquitination and subsequent degradation of the target protein by the proteasome . More than 15 PROTAC degraders are in or approaching the clinic currently , against a variety of targets, including hormone receptors (e.g. AR and ER), transcription factor (e.g. STAT3), anti-apoptotic protein (e.g. BCL-XL), kinases (e.g. BTK and IRAK4), and epigenetic proteins (e.g. BRD9). PROTAC is not only an emerging drug discovery modality but also offers new chemical tools for target identification and validation, and for deciphering target biology . For example, PROTAC-mediated degradation can reveal noncatalytic activity of protein kinases . Herein, we report the discovery and characterization of XL01126, a von Hippel-Lindau (VHL)-based, fast, potent, cooperative and selective LRRK2 PROTAC degrader that is also orally bioavailable and blood brain barrier (BBB) permeable. XL01126 qualifies as a chemical probe to study LRRK2 biology, further validate the target as a therapeutic concept in PD, and usher future drug development.