How Your Cells Take Out the Trash — And Why One Tiny Protein Matters

USU Researchers Uncover the Role of TMED9 in Protecting Cells from Misfolded Proteins, critical for cell health and preventing disease.

USU study co-authors Dr. Elsa Ronzier (left) and Dr. Prasanna Satpute-Krishnan (right), with
Neuroscience graduate student Alexandra Graninger, in Dr. Krishnan’s lab at USU. 
(Photo by Thomas Balfour)

May 5, 2025 by Sharon Holland

Have you ever wondered how your body knows when something isn’t working right—and what it does about it? Deep inside our cells, there's a surprisingly complex and efficient system for handling "mistakes," especially when it comes to proteins. Proteins form tiny machines that do most of the work in our bodies, but they only work properly if they’re folded into the right shape. When that folding goes wrong, the cell has to step in fast—because misfolded proteins can cause all kinds of trouble, including serious diseases.

A recent study, “TMED9 coordinates the clearance of misfolded GPI-anchored proteins out of the ER and into the Golgi,” published in PLOS Biology April 9, 2025, by Uniformed Services University (USU) researchers shines a spotlight on one of the unsung heroes of this cleanup crew: a protein called TMED9. Think of TMED9 as a kind of quality control supervisor—one that helps spot defective proteins and get them out of the way before they can cause damage.

Some proteins, known as GPI-anchored proteins, are supposed to be sent to the surface of the cell where they help with communication and defense. But like any manufacturing process, things can go wrong. If these proteins don’t fold correctly, they get stuck in a part of the cell called the endoplasmic reticulum (ER)—basically, a protein assembly line.

This is where TMED9 comes in. When the ER is under stress and starts producing too many faulty proteins, an ER-clearance system called RESET (Rapid ER Stress-Induced Export) kicks in. TMED9 helps grab the bad proteins and move them to another part of the cell, the Golgi, where they can be marked for disposal.

The researchers, Dr. Prasanna Satpute-Krishnan, assistant professor, and Dr. Elsa Ronzier, a former scientist, in the Department of Biochemistry and Molecular Biology at USU, discovered that when TMED9 isn’t working—either because it’s blocked or removed—those misfolded proteins can’t leave the ER assembly line. They pile up, putting the cell under even more stress. On the flip side, if TMED9 is restored, the RESET system starts working again, almost like hitting the reset button on your phone when it’s acting up. 

Even more fascinating? TMED9 doesn’t interfere with the healthy proteins that are folded correctly. It seems to be a specialist—only stepping in when there’s a problem.

TMED9 doesn’t work alone. It has a few partners—other proteins with names like TMP21 and TMED2—that help it get the job done. Together, they act like a finely tuned cleanup crew, making sure the cell stays healthy and focused on its real work.

While this might seem like microscopic housekeeping, it’s actually a big deal. When the body can’t get rid of bad proteins properly, it can lead to a number of serious conditions, including neurodegenerative diseases like Alzheimer’s. By better understanding how TMED9 and the RESET system work, scientists hope to find new ways to treat or even prevent some of these diseases.

In the end, TMED9 is basically the cellular janitor-slash-bouncer—tossing out troublemakers and keeping the place running like a well-oiled machine. Without it, your cells would be a microscopic mess hall after a food fight.