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NaV1.5 is distributed in a specific pattern at the plasma membrane of cardiomyocytes, with localization at the crests, grooves, and T-tubules of the lateral membrane and particularly high levels at the intercalated disc region. NaV1.5 forms a large macromolecular complex with and is regulated by interacting proteins, some of which are specifically localized at either the lateral membrane or intercalated disc. One of the NaV1.5 trafficking routes is via microtubules (MTs), which are regulated by MT plus-end tracking proteins (+TIPs). In our search for mechanisms involved in targeted delivery of NaV1.5, we here provide an overview of previously demonstrated interactions between NaV1.5 interacting proteins and +TIPs, which potentially (in)directly impact on NaV1.5 trafficking. Strikingly, +TIPs interact extensively with several intercalated disc- and lateral membrane-specific NaV1.5 interacting proteins. Recent work indicates that this interplay of +TIPs and NaV1.5 interacting proteins mediates the targeted delivery of NaV1.5 at specific cardiomyocyte subcellular domains, while also being potentially relevant for the trafficking of other ion channels. These observations are especially relevant for diseases associated with loss of NaV1.5 specifically at the lateral membrane (such as Duchenne muscular dystrophy), or at the intercalated disc (for example, arrhythmogenic cardiomyopathy), and open up potential avenues for development of new anti-arrhythmic therapies.<\/jats:p>","DOI":"10.1093\/cvr\/cvad052","type":"journal-article","created":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T20:22:04Z","timestamp":1681244524000},"page":"1461-1479","source":"Crossref","is-referenced-by-count":11,"title":["Microtubule plus-end tracking proteins: novel modulators of cardiac sodium channels and arrhythmogenesis"],"prefix":"10.1093","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7353-0235","authenticated-orcid":false,"given":"Gerard A","family":"Marchal","sequence":"first","affiliation":[{"name":"Department of Experimental Cardiology, Heart Centre, Amsterdam UMC location University of Amsterdam , Meibergdreef 9, 1105 AZ Amsterdam , The Netherlands"},{"name":"Amsterdam Cardiovascular Sciences, Heart Failure & Arrhythmias , Meibergdreef 9, 1105 AZ Amsterdam , The Netherlands"},{"name":"European Laboratory for Non-Linear Spectroscopy (LENS), and National Institute of Optics (CNR-INO), Sesto Fiorentino , Via Nello Carrara 1, 50019, Florence , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1964-3607","authenticated-orcid":false,"given":"Niels","family":"Galjart","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Erasmus University Medical Center , Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7221-859X","authenticated-orcid":false,"given":"Vincent","family":"Portero","sequence":"additional","affiliation":[{"name":"Department of Experimental Cardiology, Heart Centre, Amsterdam UMC location University of Amsterdam , Meibergdreef 9, 1105 AZ Amsterdam , The Netherlands"},{"name":"Amsterdam Cardiovascular Sciences, Heart Failure & Arrhythmias , Meibergdreef 9, 1105 AZ Amsterdam , The Netherlands"},{"name":"Laboratory of Experimental Cardiology, Department of Cardiology, Leiden University Medical Center (LUMC) , Leiden , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0095-0084","authenticated-orcid":false,"given":"Carol Ann","family":"Remme","sequence":"additional","affiliation":[{"name":"Department of Experimental Cardiology, Heart Centre, Amsterdam UMC location University of Amsterdam , Meibergdreef 9, 1105 AZ Amsterdam , The Netherlands"},{"name":"Amsterdam Cardiovascular Sciences, Heart Failure & Arrhythmias , Meibergdreef 9, 1105 AZ Amsterdam , The 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