Restoring enzyme involved in cellular cleanup could reduce inflammation and scarring from liver disease MASH

Ekihiro Seki remembers the exact moment his team saw the damaged mitochondria piling up in liver cells like broken engines in a stalled factory. It was a clue that led them to an enzyme called UBE2N, hiding in plain sight, protecting livers from one of the most common — and silent — diseases in America. Now, their work at Cedars-Sinai in Los Angeles suggests this tiny biological helper could be key to stopping fatty liver disease before it turns deadly.

Right now, about 100 million people in the U.S. are living with metabolic dysfunction-associated steatotic liver disease (MASLD), a condition where fat builds up in the liver, often without symptoms. For up to 1 in 4, it can worsen into MASH — a more dangerous form marked by inflammation, scarring, and lasting damage. With no approved cure and few effective drugs, doctors mostly recommend diet and exercise. But what if a simple enzyme could do more?

Seki and his team discovered that as liver disease gets worse, levels of UBE2N drop sharply. This enzyme isn’t just a bystander — it helps clear out damaged mitochondria, the power plants inside our cells. When those broken parts aren’t removed, they trigger inflammation and cell death, fueling the fire of MASH. In mice with restored UBE2N levels, the results were striking: less fat, less scarring, and calmer immune responses. The liver began to heal itself.

This isn’t just about one protein. It’s about a whole cleanup system gone wrong. The study, published in Nature Metabolism, shows UBE2N works through a pathway involving another protein called p62, which acts like a tag for damaged parts. Without enough UBE2N, the tagging system fails, and junk piles up. Restoring the enzyme fixed the chain reaction.

The impact could be huge. If future therapies can boost UBE2N in humans, they might stop MASH before patients need transplants. "The UBE2N enzyme appears to protect the liver from the inflammation and damage associated with MASH by helping remove damaged mitochondria and supporting the breakdown of fat," said Seki, who co-led the study. That insight gives researchers a new target — not just to slow the disease, but possibly reverse it.

Now, the focus shifts to turning these findings into real treatments. Scientists will look for ways to activate UBE2N safely in people, test who might benefit most, and explore whether combining this approach with lifestyle changes boosts results. For millions at risk, the path to healthier livers may start with a single enzyme.