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Accumulating evidence suggests that there are phenotypic, neuropathologic, and biological similarities between sporadic PD (sPD) and familial forms in which\n                    <jats:italic>LRRK2<\/jats:italic>\n                    variants are inherited in an autosomal\u2010dominant pattern with variable penetrance (LRRK2\u2010PD). Further, genome\u2010wide association studies have found specific non\u2010coding variants that are risk factors for sPD. In this review, we describe the current state of knowledge as it relates to LRRK2's role in sPD, with a focus on comparing the physiology and pathology of sPD with LRRK2\u2010PD. As in LRRK2\u2010PD, LRRK2 activity may also be increased in sPD, possibly through interactions between genetics and the environment. Increased activity of LRRK2 and associated endolysosomal dysfunction have been observed in sPD patients, including evidence from postmortem brains of patients with sPD and animal models showing increased LRRK2 activity. Additionally, beneficial effects of LRRK2 inhibitors, such as improved lysosomal function, reduced \u03b1\u2010synuclein accumulation, and amelioration of neurodegeneration, have been demonstrated in animal models of sPD. Therefore, inhibition of LRRK2 kinase activity may be a promising approach to disease modification for sPD and LRRK2\u2010PD. Ongoing and future clinical studies examining LRRK2 kinase inhibitors will aim to elucidate their clinical efficacy in PD and to assess their potential effects on lysosomal function. \u00a9 2025 The Author(s).\n                    <jats:italic>Movement Disorders<\/jats:italic>\n                    published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n                  <\/jats:p>","DOI":"10.1002\/mds.70100","type":"journal-article","created":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T05:35:33Z","timestamp":1765604133000},"page":"297-314","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["<scp>LRRK2<\/scp>\n                    as a Potential Disease\u2010Modifying Target in Sporadic Parkinson's Disease"],"prefix":"10.1002","volume":"41","author":[{"given":"Anthony E.","family":"Lang","sequence":"first","affiliation":[{"name":"Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital and Edmond J. Safra Program in Parkinson Disease University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6369-1203","authenticated-orcid":false,"given":"Robert A.","family":"Hauser","sequence":"additional","affiliation":[{"name":"Parkinson's Disease and Movement Disorders Center University of South Florida  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9384-1305","authenticated-orcid":false,"given":"Lorraine V.","family":"Kalia","sequence":"additional","affiliation":[{"name":"Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital and Edmond J. Safra Program in Parkinson Disease University of Toronto  Toronto Ontario Canada"},{"name":"Division of Neurology, Department of Medicine, Tanz Centre for Research in Neurodegenerative Diseases University of Toronto  Toronto Ontario Canada"},{"name":"Krembil Research Institute, Toronto Western Hospital University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonnie","family":"Hersh","sequence":"additional","affiliation":[{"name":"Biogen Inc.  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zdenek","family":"Berger","sequence":"additional","affiliation":[{"name":"Biogen Inc.  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy Llorens","family":"Arenas","sequence":"additional","affiliation":[{"name":"Biogen Inc.  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coro","family":"Paisan\u2010Ruiz","sequence":"additional","affiliation":[{"name":"Biogen Inc.  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle","family":"Fraser","sequence":"additional","affiliation":[{"name":"Biogen Inc.  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0753-6281","authenticated-orcid":false,"given":"Danna","family":"Jennings","sequence":"additional","affiliation":[{"name":"Denali Therapeutics  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jillian H.","family":"Kluss","sequence":"additional","affiliation":[{"name":"Denali Therapeutics  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Huntwork\u2010Rodriguez","sequence":"additional","affiliation":[{"name":"Denali Therapeutics  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia G.","family":"Henry","sequence":"additional","affiliation":[{"name":"Denali Therapeutics  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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