STAT+: How a global effort to explore the ‘dark proteome’ is upending our understanding of human disease

STAT PlusIn the Lab How a global effort to explore the ‘dark proteome’ is upending our understanding of human disease Scientists discover novel microproteins involved in gene regulation, immune responses, and cancer Manage alerts for this article Email this article Share this article By Megan MolteniMay 6, 2026 Science Writer Megan Molteni[email protected]Megan Molteni reports on discoveries from the frontiers of genomic medicine, neuroscience, and reproductive tech. She joined STAT in 2021 after covering health and science at WIRED. You can reach Megan on Signal at mmolteni.13.

In 2019, Sebastiaan van Heesch was trying to pry apart the secrets of a broken heart. A systems biologist, van Heesch used a newish method to analyze the contents of ribosomes, cellular protein factories, in a collection of frozen hearts donated by 80 people, many of whom had died from end-stage heart failure. By uncovering all the proteins being produced in each heart, he and his team hoped to learn what had gone wrong.

What they found with this “ribosome profiling” tool produced more questions than answers. In addition to proteins encoded by known genes, the ribosomes also seemed to be making hundreds of never-before-seen mini-proteins — molecules just a few dozen amino acids long whose code could be traced back to portions of the genome that weren’t thought to produce proteins. The main destination for many of these “dark proteins” was the mitochondria, raising the possibility that they were influencing the energy production process necessary for the muscles of the heart to beat properly.Advertisement “All of a sudden we could look at all of these noncoding RNAs getting translated,” van Heesch said.

“All of these weird things we didn’t know were happening before suddenly became visible.” STAT+ Exclusive Story Already have an account? Log in This article is exclusive to STAT+ subscribers Unlock this article — plus in-depth analysis, newsletters, premium events, and news alerts. Already have an account?

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Subscribe Log In Cancer, genetics, research, STAT+ Submit a correction requestReprints Megan Molteni Science Writer Megan Molteni reports on discoveries from the frontiers of genomic medicine, neuroscience, and reproductive tech. She joined STAT in 2021 after covering health and science at WIRED. You can reach Megan on Signal at mmolteni.13.

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