Surreal illustration of a cell with DNA and cholesterol molecule, representing UBXD8's role in cholesterol regulation.

Decoding Cholesterol: How UBXD8 Impacts Your Health and Statins

Rhea Morgan in Health & Wellness July 2025 • 4 min read.

"New research reveals a crucial gene's role in cholesterol management, offering insights for statin users and those seeking metabolic balance."

Cholesterol, often portrayed negatively, is vital for cell membranes and hormone production. The body tightly regulates its cholesterol levels through a complex process called the mevalonate pathway. A key enzyme in this pathway, HMGCR, is the target of statin drugs, commonly prescribed to lower cholesterol. Understanding how HMGCR is regulated is crucial for maintaining metabolic health.

The regulation of HMGCR is a balancing act, responding to both increasing and decreasing signals. When cholesterol levels get too high, the body triggers a process to break down HMGCR, reducing cholesterol production. Scientists have long sought to understand the genetic factors controlling this breakdown, known as degradation.

Now, a groundbreaking study has identified a previously unknown player in this process: the UBXD8 gene. This discovery sheds light on how our bodies manage cholesterol and could have implications for how we use statins and approach metabolic health.

The UBXD8 Discovery: A New Piece in the Cholesterol Puzzle

Surreal illustration of a cell with DNA and cholesterol molecule, representing UBXD8's role in cholesterol regulation.

Researchers used an innovative genetic screening technique to pinpoint genes involved in HMGCR regulation. They modified human cells to glow when HMGCR was present, then used this system to identify genes that, when disrupted, altered HMGCR levels. This approach led them to UBXD8, a gene not previously linked to cholesterol metabolism.

The study revealed that UBXD8 is essential for the sterol-stimulated degradation of HMGCR. When UBXD8 is absent, the body loses its ability to effectively break down HMGCR when cholesterol levels are high, leading to an overproduction of cholesterol. This was demonstrated in multiple cell types, highlighting the broad relevance of this gene.

Key Finding: UBXD8 is a critical determinant in the metabolic breakdown of HMGCR, a key step in cholesterol regulation.
Metabolic Imbalance: Without UBXD8, cells lose proper cholesterol feedback control, leading to excessive synthesis.
Multiple Cell Types: This regulatory role was confirmed across various cell types, including liver cells.

Further investigation showed that UBXD8 helps move HMGCR from its location in the endoplasmic reticulum (ER) to the cellular machinery responsible for breaking it down. This movement, called dislocation, is a critical step in HMGCR degradation and requires a specific part of the UBXD8 protein called the UBX domain.

What This Means for You: UBXD8, Statins, and Future Therapies

This discovery opens new avenues for understanding and potentially treating cholesterol imbalances. While more research is needed, here are some key takeaways:

The UBXD8 gene's impact on cholesterol regulation suggests potential for future therapies targeting this pathway. For instance, understanding how to enhance UBXD8 function could provide a new approach to lowering cholesterol.

This research demonstrates the power of genetic screening for unraveling complex metabolic processes. By identifying key regulators like UBXD8, scientists can gain deeper insights into maintaining health and combating disease.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1161/atvbaha.117.310002, Alternate LINK

Title: Haploid Mammalian Genetic Screen Identifies Ubxd8 As A Key Determinant Of Hmgcr Degradation And Cholesterol Biosynthesis

Subject: Cardiology and Cardiovascular Medicine

Journal: Arteriosclerosis, Thrombosis, and Vascular Biology

Publisher: Ovid Technologies (Wolters Kluwer Health)

Authors: Anke Loregger, Matthijs Raaben, Josephine Tan, Saskia Scheij, Martina Moeton, Marlene Van Den Berg, Hila Gelberg-Etel, Elmer Stickel, Joseph Roitelman, Thijn Brummelkamp, Noam Zelcer

Published: 2017-11-01

Everything You Need To Know

What is the role of the UBXD8 gene in cholesterol management?

The UBXD8 gene plays a crucial role in the breakdown of the HMGCR enzyme, which is a key target of statin drugs. When cholesterol levels are high, UBXD8 facilitates the movement of HMGCR from the endoplasmic reticulum to cellular machinery for degradation. Without UBXD8, the body's ability to reduce cholesterol production is impaired. This means cells lose proper cholesterol feedback control, leading to excessive cholesterol synthesis.

How does the UBXD8 gene relate to statin drugs and their function?

Statin drugs work by inhibiting the HMGCR enzyme, which is involved in cholesterol production through the mevalonate pathway. The UBXD8 gene is essential for the sterol-stimulated degradation of HMGCR. While statins directly inhibit HMGCR, UBXD8 helps in removing HMGCR when cholesterol levels are already high. The interplay between statins and UBXD8 suggests that UBXD8 could potentially enhance the effectiveness of statin treatments.

How does UBXD8 facilitate the movement of HMGCR from the endoplasmic reticulum (ER) to degradation machinery?

The endoplasmic reticulum (ER) is where HMGCR resides, and UBXD8 helps move HMGCR from the ER to the cellular machinery for degradation. This movement, referred to as dislocation, is critical for breaking down HMGCR when cholesterol levels are high. The UBX domain of the UBXD8 protein is essential for this process. Without UBXD8 facilitating this movement, HMGCR is not effectively broken down, leading to overproduction of cholesterol.

How does the UBXD8 gene influence the mevalonate pathway?

The mevalonate pathway is a complex process that regulates cholesterol levels in the body. HMGCR is a key enzyme in this pathway and the target of statin drugs. The UBXD8 gene influences cholesterol biosynthesis and degradation by playing a role in the breakdown of HMGCR. By understanding how UBXD8 affects the mevalonate pathway, scientists can gain insights into maintaining metabolic health and potentially enhancing the effectiveness of statin treatments.

How was the UBXD8 gene discovered to be involved in cholesterol regulation?

Researchers identified the UBXD8 gene using an innovative genetic screening technique. They modified human cells to glow when HMGCR was present, then used this system to identify genes that, when disrupted, altered HMGCR levels. This approach led them to UBXD8, a gene not previously linked to cholesterol metabolism. This method allowed them to pinpoint genes involved in HMGCR regulation, leading to the discovery of UBXD8's role in cholesterol management.