Phospholamban mRNA (PLN mRNA)

Phospholamban (PLN) mRNA is the transcript encoding the phospholamban protein, a 52-amino acid micropeptide that serves as a critical regulator of the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a) in cardiac muscle. In its dephosphorylated state, the PLN protein physically interacts with and inhibits SERCA2a, thereby controlling the rate of calcium reuptake into the sarcoplasmic reticulum and influencing cardiac relaxation (lusitropy) and contractility (inotropy). Mutations in the PLN gene, most notably the R14del (arginine 14 deletion) variant, lead to the production of dysfunctional mRNA and protein that aggregate and cause severe inherited dilated cardiomyopathy and heart failure. Therapeutic strategies targeting PLN mRNA, such as antisense oligonucleotides (ASOs) and RNA interference (RNAi), aim to selectively downregulate the expression of the inhibitory or toxic protein to restore calcium homeostasis and improve cardiac performance. While preclinical models show promise, a significant therapeutic challenge is the potential for lethal cardiomyopathy observed in humans with complete PLN deficiency, necessitating precise dosing to achieve partial knockdown.

Other names

Phospholamban messenger RNAPLB mRNACardiac phospholamban mRNACMD1P mRNACMH18 mRNA

Antisense oligonucleotide-mediated mRNA degradation and protein knockdown