Table 1.

Publications on SERCA Function in Different Models for PLN-R14del Cardiomyopathy

Year	Group	Model	Speciesa	PLN-R14del Effect on SERCA Function	Ref. #
2006	Kranias	Transgenic PLN-R14del mouse	M	SERCA superinhibition when WT-PLN is present.	2
		HEK-293 cells	H	SERCA superinhibition when WT-PLN is present.
2012	Kranias	R14del mouse model in PLN-KO background	M	No SERCA superinhibition in absence of WT-PLN.	18
2012	Young	Proteoliposomes	H	Partial loss-of-function in presence and absence of WT-PLN.	28
2014	Middleton	Phospholipid membranes	H	Reduced inhibitory effect on SERCA.	29
2015	Veglia	DPC-d38 micelles and lipid membranes	H	Loss-of-function mutant (compared to WT-PLN).	30
2021	Hansen	hiPSC-CMs	H	SERCA function largely unaffected.	27
2021	Zaza	hiPSC-CMs	H	Loss-of-function.	24
2021	Bakkers	PLN-R14del zebrafish	Z	Longer Ca2+ transients and slower decay (indicative of enhanced SERCA inhibition).	25
2021	Kranias	hPLN-R14del mouse	H	Prolonged τ in RV (not LV) cardiomyocytes, indicative of enhanced SERCA inhibition. The propensity to arrhythmia may be increased.	19
2022	Kranias and Sanoudou	hPLN-R14del mouse	H	Increased binding to SERCA and HAX-1, which may enhance SERCA inhibition (not directly tested).	42
2023	Kranias and Sadayappan	hPLN-R14del mouse	H	Prolonged τ in RV cardiomyocytes (indicative of enhanced SERCA inhibition). Normal calcium handling in LV cardiomyocytes.	20
2023	Zaza	PLN-R14Δ/+mouse	M	Loss-of-function.	23
2023	Silljé	PLN-R14Δ/Δand R14Δ/+mouse	M	Enhanced calcium reuptake.	5
2023	Robia	HEK-293 cells	H	Loss-of-function via PLN pentamer stabilization and decreased binding affinity for SERCA.	37

Bold represents data indicative of PLN loss-of-function of SERCA inhibition (either partial or complete); italic represents data indicative of SERCA superinhibition.

Ca²⁺ = calcium; DPC-d38 = dodecylphosphocholine-d38; H = human; HAX-1 = HS-1-associated protein X-1; HEK-293 cells = human embryonic kidney 293 cells; hiPSC-CMs = human induced pluripotent stem cell–derived cardiomyocytes; hPLN-R14del mouse = humanized PLN-R14del mouse model; KO = knockout; LV left ventricle; M = mouse, PLN = phospholamban; PLN-R14^Δ/+ mouse = heterozygous PLN-R14del knock-in mouse model; PLN-R14^Δ/Δ mouse = homozygous PLN-R14del knock-in mouse model; RV = right ventricle; SERCA = sarco/endoplasmic reticulum calcium adenosine triphosphatase; WT = wild type; Z = zebrafish.

^aSpecies column indicates from which species the used PLN-R14del sequence originates.