{"doi":"10.1016/j.jacbts.2024.02.017","title":"Reassessing the Mechanisms of PLN-R14del Cardiomyopathy","abstract":"The phospholamban (PLN) pathogenic gene variant, p.Arg14del (PLN-R14del), can lead to dilated and arrhythmogenic cardiomyopathy, resulting in heart failure. PLN-R14del cardiomyopathy has been conceptualized as a disease caused by sarco/endoplasmic reticulum calcium adenosine triphosphatase 2a (SERCA2a) superinhibition. However, recent studies raised controversy regarding the effect of PLN-R14del on SERCA activity and revealed a prominent role for abnormal PLN protein distribution and sarco/endoplasmic reticulum disorganization as underlying disease mechanism. Strategies targeting sarco/endoplasmic reticulum malformation may, therefore, prove more effective than SERCA activity modulation. This review reassesses the disease mechanisms of PLN-R14del cardiomyopathy and emphasizes the importance of dissecting the underlying molecular mechanisms to uncover targets for innovative treatments.","journal":"JACC Basic to Translational Science","year":2024,"id":423280,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9579,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":55735,"name":"Rudolf A. de Boer","orcid":"0000-0002-4775-9140","position":1,"is_corresponding":false},{"id":350049,"name":"Catherine A. Makarewich","orcid":"0000-0001-6907-4401","position":2,"is_corresponding":false},{"id":489061,"name":"Peter van der Meer","orcid":"0000-0002-9705-4413","position":3,"is_corresponding":false},{"id":55715,"name":"Herman H.W. Silljé","orcid":"0000-0003-3292-6302","position":4,"is_corresponding":false},{"id":1218363,"name":"Nienke M. Stege","orcid":"0000-0002-7658-9291","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-19T01:57:56.814994Z","pmid":"39297138","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}