{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:53:57Z","timestamp":1787018037082,"version":"build-2736575974"},"reference-count":94,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:p>The discovery of the PLN-R14del (deletion of arginine 14 [p.Arg14del] within the phospholamban protein) genetic mutation, characterized by a deletion of R14 in phospholamban, in a large Greek family marked a significant milestone in understanding the cause of its associated cardiomyopathy. Since its initial identification in 2006, this mutation has been found in numerous patients across 11 countries. PLN-R14del carriers commonly exhibit both dilated cardiomyopathy and arrhythmogenic cardiomyopathy, accounting for a significant portion of annual heart transplants in the Netherlands. Under physiological conditions, PLN plays a crucial role in regulating the calcium pump SERCA2a (sarco[endo]plasmic reticulum calcium ATPase 2a) within cardiomyocytes. While the normal function of PLN has been extensively studied, the precise mechanisms underlying the pathogenesis of PLN-R14del\u2013induced heart disease remain uncertain and subject to ongoing debate. The current review systematically summarizes existing literature on the PLN-R14del mutation, elucidating its pathological phenotypes and discussing its implications in PLN-R14del cardiomyopathy. Current knowledge is consolidated, and unresolved questions are addressed with the aim to contribute to a deeper understanding of PLN-R14del\u2013associated cardiac pathology. Finally, this review provides guidance for future research to advance diagnosis and therapeutic approaches for affected individuals.<\/jats:p>","DOI":"10.1161\/circheartfailure.124.012661","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T09:00:45Z","timestamp":1758704445000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Unraveling the Pathophysiological Mechanisms of Phospholamban R14del Cardiomyopathy: A Comprehensive Overview"],"prefix":"10.1161","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6607-4104","authenticated-orcid":true,"given":"Renee G.C.","family":"Maas","sequence":"first","affiliation":[{"name":"Utrecht Regenerative Medicine Center, Circulatory Health Research Center, University Utrecht, the Netherlands (R.G.C.M., J.A.B., J.P.G.S., F.S.)."},{"name":"Department of Cardiology, Experimental Cardiology Laboratory, University Medical Center Utrecht, 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