Phospholamban

Where it comes from

Made in

Heart muscle, and slow skeletal and smooth muscle

Sent out by

Not secreted; adrenaline’s receptor phosphorylates it, which lifts its brake on the pump

Acts on

• SERCA2a

What it does

• Slows calcium reuptake at rest, which keeps the heartbeat modest
• Phosphorylated under adrenaline, it lets go and the heart beats harder and faster
• The main way the sympathetic system speeds relaxation

In medicine

• Mutations (R14del in the Netherlands, L39X, R9C) cause dilated and arrhythmogenic cardiomyopathy and sudden death; R14del is a Dutch founder variant and carriers develop both pictures at once ¹
• Testing for them is part of cardiomyopathy gene panels

Beyond the body’s own use

• The first trial of a drug meant to lower phospholamban production began in December 2025: a phase 1 single-dose study in 23 R14del carriers, measuring the amount of PLN messenger RNA in heart biopsies alongside safety ³
• The animal work behind it is strong. In mice carrying the same change, an injected antisense drug stopped the protein clumping, held off the failing of the heart and tripled survival ²
• Gene therapy and gene editing for R14del remain in animals, and the opposite approach, raising the pump this protein brakes with an AAV gene therapy, missed its endpoints in people with heart failure in 2016 ⁴