biostudies-literatureVafiadaki ECURE-PLaN, a grant from the Leducq Foundation for Cardiovascular Research1162205https://www.ebi.ac.uk/biostudies/studies/S-EPMC10151546biostudies-literatureUnknown10Arrhythmogenic cardiomyopathy affects significant number of patients worldwide and is characterized by life-threatening ventricular arrhythmias and sudden cardiac death. Mutations in multiple genes with diverse functions have been reported to date including phospholamban (PLN), a key regulator of sarcoplasmic reticulum (SR) Ca²⁺ homeostasis and cardiac contractility. The PLN-R14del variant in specific is recognized as the cause in an increasing number of patients worldwide, and extensive investigations have enabled rapid advances towards the delineation of PLN-R14del disease pathogenesis and discovery of an effective treatment. We provide a critical overview of current knowledge on PLN-R14del disease pathophysiology, including clinical, animal model, cellular and biochemical stuFrontiers in cardiovascular medicinePhospholamban R14del disease: The past, the present and the future.PMC1015154618CVD01Vafiadaki ESanoudou DDoevendans PAKranias EGGlijnis PCfalsePhospholamban R14del disease: The past, the present and the future.Arrhythmogenic cardiomyopathy affects significant number of patients worldwide and is characterized by life-threatening ventricular arrhythmias and sudden cardiac death. Mutations in multiple genes with diverse functions have been reported to date including phospholamban (PLN), a key regulator of sarcoplasmic reticulum (SR) Ca²⁺ homeostasis and cardiac contractility. The PLN-R14del variant in specific is recognized as the cause in an increasing number of patients worldwide, and extensive investigations have enabled rapid advances towards the delineation of PLN-R14del disease pathogenesis and discovery of an effective treatment. We provide a critical overview of current knowledge on PLN-R14del disease pathophysiology, including clinical, animal model, cellular and biochemical stu2023-01-01T00:00:00Z20232025-04-04T10:20:16.721Z2025-02-19T00:12:23.732ZS-EPMC101515463714405610.3389/fcvm.2023.1162205