How TMEM251 gene changes cause a severe lysosomal storage disorder

Characterization of TMEM251 that causes a new type of severe lysosome storage disease

NIH-funded research University of Michigan at Ann Arbor · NIH-11179418

This project looks at how changes in the TMEM251 gene cause a severe lysosomal storage disease that leads to bone and heart problems in affected children.

Quick facts

Grant typeR01 grant
Study typeNIH-funded research
Funding institutionUniversity of Michigan at Ann Arbor NIH-funded
Lab location1 site (Ann Arbor, United States)
Project IDNIH-11179418 on NIH RePORTER

What this research studies

From a patient's point of view, the team is tracing how TMEM251 problems make lysosomes fail so enzymes meant to work inside cells instead leak into the blood. They use gene editing (CRISPR) in human cells and create zebrafish models to see how losing TMEM251 changes development and causes the bone and heart problems seen in patients. The researchers measure enzyme secretion, look for buildup of undigested material in lysosomes, and study the molecular steps that go wrong in the cell. The goal is to link the genetic change to specific cellular failures that explain patient symptoms.

Who could benefit from this research

Good fit: Ideal candidates are people (often children) who have early-onset skeletal dysplasia, short stature, cardiomyopathy, or a confirmed or suspected TMEM251 mutation.

Not a fit: People without TMEM251 mutations or with unrelated medical conditions are unlikely to benefit directly from this project.

Why it matters

Potential benefit: If successful, this work could improve diagnosis and point to targets for future treatments for people with TMEM251-related lysosomal disease.

How similar studies have performed: Genetic and animal-model studies have explained other lysosomal storage diseases and helped guide therapies, but TMEM251 is newly linked to this severe form and the work is still early-stage.

Where this research is happening

Ann Arbor, United States

Researchers

About this research

  1. This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
  2. Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
  3. For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.