Peptide directoryBone, muscle & mineral

DWORF

A tiny peptide that speeds the heart’s calcium pump by pushing its brake aside.

Where it comes from

Made in
Heart muscle, and slow-twitch skeletal muscle
Sent out by
Not secreted
Acts on
  • SERCA2a in heart muscle

What it does

  • Makes calcium return faster, so the heart relaxes and refills better 1
  • Reduced in failing hearts 2
  • Found in 2016 by the same group that found myoregulin, in a transcript everyone had filed as non-coding 1

In medicine

  • No medicine acts on it, no human disease has been traced to its gene, and it appears on no gene panel
  • Its interest to the clinic is as a counterweight: the amount of it falls in failing human heart muscle, alongside the slow calcium handling that marks heart failure 2

Beyond the body’s own use

  • Delivered by gene therapy it rescued heart function and survival in mice with dilated cardiomyopathy and in the Duchenne heart, and a 2025 study added better mitochondrial function to the list 23
  • Its appeal over boosting the pump directly is that one small peptide lifts three brakes at once; whether a 35-residue peptide can be dosed in a person, or has to be delivered as a gene, is untested
  • Nothing has reached a human trial, and the caution is next door: the one attempt to raise this same pump in people, an AAV gene therapy for heart failure, missed its endpoints in 2016 4

Sources

  1. Nelson et al., A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity, Science 2016
  2. Makarewich et al., The DWORF micropeptide enhances contractility and prevents heart failure in mice, eLife 2018
  3. Brito-Estrada et al., DWORF gene therapy improves cardiac calcium handling and mitochondrial function, Circulation Research 2025
  4. Greenberg et al., Calcium upregulation by gene therapy in cardiac disease (CUPID 2), The Lancet 2016

This card describes what a medicine is for and what the evidence says; it recommends nothing. Talk to your clinician about anything you read here.