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Recent studies have identified proprotein convertase subtilisin\/kexin type 9 (PCSK9) as a pivotal mediator in the pathogenesis of DCM. PCSK9 contributes not only to dyslipidemia via degradation of LDLR and consequent elevation of circulating LDL-C, but also to metabolic derangements and inflammation through interactions with receptors such as CD36 and Toll-like receptor 4 (TLR4). In DCM, PCSK9 has been shown to exacerbate inflammation and pyroptosis and is closely linked to impaired autophagic function. Elevated circulating PCSK9 has emerged as a potential biomarker for cardiovascular events in patients with type 2 diabetes mellitus (T2DM). At the same time, long-term administration of PCSK9 inhibitors (PCSK9i) has not been associated with a significant increase in incident diabetes. Furthermore, PCSK9 loss-of-function mutations have been linked to a modestly heightened risk of T2DM, underscoring its complex involvement in cardiometabolic regulation and disease. This review synthesizes current insights into the mechanistic and therapeutic roles of PCSK9 in DCM, aiming to inform precision cardiovascular risk management strategies in T2DM populations.<\/jats:p>","DOI":"10.3390\/biom15091240","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T09:58:32Z","timestamp":1756288712000},"page":"1240","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Impact of PCSK9 on Diabetic Cardiomyopathy: Mechanisms and Implications"],"prefix":"10.3390","volume":"15","author":[{"given":"Haixia","family":"Wang","sequence":"first","affiliation":[{"name":"The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Wang","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yubo","family":"Wang","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuzhen","family":"Du","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Heart Center, The First Hospital of Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Heart Center, The First Hospital of Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"109119","DOI":"10.1016\/j.diabres.2021.109119","article-title":"IDF Diabetes Atlas: Global, Regional and Country-Level Diabetes Prevalence Estimates for 2021 and Projections for 2045","volume":"183","author":"Sun","year":"2022","journal-title":"Diabetes Res. 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