Phospholamban (PLN) is a cardiac micropeptide that reversibly inhibits the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a), thereby regulating calcium homeostasis and cardiac contractility 1. PLN binds preferentially to the ATP-bound E1 form of SERCA2a during diastole and decreases the enzyme's calcium affinity by disrupting ATP-mediated allosteric activation 1. PLN phosphorylation relieves this inhibition, allowing physiological regulation of cardiac muscle contraction in response to stimuli. The degree of SERCA2a inhibition depends on PLN's oligomeric state 1. Beyond cardiac muscle, PLN shares functional similarity with sarcolipin and myoregulin in regulating calcium uptake in the sarcoplasmic reticulum 2. Dysregulation of the SERCA-PLN axis is increasingly recognized as a pathogenic mechanism in cardiometabolic diseases, including heart failure and metabolic dysfunction-associated fatty liver disease, where reduced SERCA activity prolongs diastolic calcium clearance and promotes pathological signaling 3. Loss-of-function PLN variants, particularly the R14del mutation, cause dilated cardiomyopathy characterized by abnormal sarcoplasmic reticulum organization and calcium handling defects 4. Therapeutic strategies targeting PLN, including antisense oligonucleotides and DWORF gene therapy, show efficacy in preclinical cardiomyopathy models by improving cardiac function and survival 5, 4.