Table 1.

Schematic overview of PLN patient mutations, the experimental models used and findings obtained regarding the cardiac pathological remodelling in human and animals

PLN Mutation	Species	Mechanism	Effect
PLN-R9C mutation [30]	Human	–	DCM, HF	Ventricular dilatation	Decreased cardiac output	Premature death
[30]	Mice	Trapped PKA & PKA-mediated PLN-P	Delayed calcium transients	DCM, HF	Premature death	–
PLN-L39 STOP mutation [31]	Human	Reduced PLN mRNA	No PLN protein	Hypertrophy, DCM, HF	–	–
[31]	HEK cells & Adult Rat CM	No SERCA inhibition by PLN	No stable PLN expression	PLN misrouted to cytosol & PM	–	–
PLN-R14Del mutation [11]	Human	–	Myocardial disarrangement	Fibrofatty replacement	ARVC	Premature death
PLN-R14Del mutation (±) [10]	HEK cells	Super inhibition SERCA	Pentamer destabilisation	Enhanced PLN-SERCA	DCM	Premature death
PLN-R14Del overexpression [10]	Mice	–	Dilatation LVW	Contractile dysfunction	Ventricular arrhythmias	–
[29]	IPS-CM	Abnormal distribution PLN to cytoplasm	Electrical instability	–	–	–
PLN-R14Del mutation (−/−) [21]	Mice	PLN-SERCA interaction/inhibition lost	Misrouted towards PM	NKA stimulation	Ventricular dilation & fibrosis	–
PLN-R25C mutation [32]	Human	–	DCM	Ventricular arrhythmias	Need for ICD implantation	–
[32]	Rat	Increased SERCA-PKA interaction	Decreased calcium transient	Increased Ca2+/CaMKII interaction	HyperP-RYR/Increased SR calcium	Increased diastolic calcium & VA

PLN phospholamban, DCM dilated cardiomyopathy, HF heart failure, PKA protein kinase A, mRNA messenger RNA, PLN-P phosphorylated PLN, HEK cells human embryonic kidney cells, CM cardiomyocytes; SERCA sarcoplasmic reticulum Ca²⁺-ATPase, PM plasma membrane, ARVC arrhythmogenic right ventricular cardiomyopathy, LVW left ventricular wall, iPS-CM induced pluripotent stem cell-derived cardiomyocytes, NKA Na⁺/K⁺-ATPase, ICD implantable cardioverter-defibrillator, CaMKII Ca²⁺/calmodulin-dependent protein kinase II, HyperP-RYR hyper-phosphorylated ryanodine receptor, VA ventricular arrhythmias