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As such, alternative strategies are needed. A promising approach is the use of molecules that reduce the function of leucine\u2010rich repeat kinase (LRRK2). Gain\u2010of\u2010function mutations in <jats:italic>LRRK2<\/jats:italic> account for a notable proportion of familial Parkinson's disease cases, and significantly, elevated LRRK2 kinase activity is reported in idiopathic Parkinson's disease. Here, we describe progress in finding therapeutically effective LRRK2 inhibitors, summarising studies that range from <jats:italic>in vitro<\/jats:italic> experiments to clinical trials. LRRK2 is a complex protein with two enzymatic activities and a myriad of functions. This creates opportunities for a rich variety of strategies and also increases the risk of unintended consequences. We comment on the strength and limitations of the different approaches and conclude that with two molecules under clinical trial and a diversity of alternative options in the pipeline, there is cause for optimism.<\/jats:p><\/jats:sec><jats:sec><jats:title>LINKED ARTICLES<\/jats:title><jats:p>This article is part of a themed issue on Building Bridges in Neuropharmacology. To view the other articles in this section visit <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v179.8\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v179.8\/issuetoc<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15575","type":"journal-article","created":{"date-parts":[[2021,5,29]],"date-time":"2021-05-29T17:28:17Z","timestamp":1622309297000},"page":"1478-1495","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["The development of inhibitors of leucine\u2010rich repeat kinase 2 (LRRK2) as a therapeutic strategy for Parkinson's disease: the current state of play"],"prefix":"10.1111","volume":"179","author":[{"given":"Sonia","family":"Azeggagh","sequence":"first","affiliation":[{"name":"School of Life, Health and Chemical Sciences The Open University  Milton Keynes UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel C.","family":"Berwick","sequence":"additional","affiliation":[{"name":"Institute of Medical and Biomedical Education St George's, University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,6,22]]},"reference":[{"key":"e_1_2_17_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2014.1973"},{"key":"e_1_2_17_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27818"},{"key":"e_1_2_17_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-013-0218-1"},{"key":"e_1_2_17_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14747"},{"key":"e_1_2_17_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25969"},{"key":"e_1_2_17_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2008.06789.x"},{"key":"e_1_2_17_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2018.04.011"},{"key":"e_1_2_17_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0453-18.2019"},{"key":"e_1_2_17_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddz271"},{"key":"e_1_2_17_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.22360"},{"key":"e_1_2_17_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23061386"},{"key":"e_1_2_17_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0080705"},{"key":"e_1_2_17_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aav0820"},{"key":"e_1_2_17_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.175"},{"key":"e_1_2_17_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi100157u"},{"key":"e_1_2_17_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds342"},{"key":"e_1_2_17_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-019-0344-2"},{"key":"e_1_2_17_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-017-0153-4"},{"key":"e_1_2_17_20_1","unstructured":"Biogen. 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