How long-term dietary cholesterol can slow down its own clearance by liver cells

RESEARCH BRIEFINGS

25 June 2026

Cholesterol carried by low-density lipoprotein (LDL) drives heart disease and is cleared by liver cells expressing the receptor LDLR. A cell-signalling mechanism has been discovered through which high cholesterol promotes the enzyme-mediated degradation of LDLR. Blocking this enzyme restores LDLR levels in liver cells, suggesting a new strategy for treating high cholesterol.

This is a summary of: Feng, X. et al. Dietary cholesterol activates a Ral-dependent pathway driving LDLR turnover. Nature https://doi.org/10.1038/s41586-026-10697-z (2026).

Access options

Access Nature and 54 other Nature Portfolio journals

Get Nature+, our best-value online-access subscription

27,99 € / 30 days

cancel any time

Subscribe to this journal

Receive 52 print issues and online access

185,98 € per year

only 3,58 € per issue

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Log in

Learn about institutional subscriptions

Read our FAQs

Contact customer support

doi: https://doi.org/10.1038/d41586-026-01899-6

‘Expert opinion’ is published under a CC BY 4.0 licence.

References

Goldstein, J. L. & Brown, M. S. Cell 161, 161–172 (2015).

Article

PubMed

Google Scholar

Luo, J., Yang, H. & Song, B.-L. Nature Rev. Mol. Cell Biol. 21, 225–245 (2020).

Article

PubMed

Google Scholar

Applebaum-Bowden, D. et al. Am. J. Clin. Nutr. 39, 360–367 (1984).

Article

PubMed

Google Scholar

Tillner, J. et al. Clin. Pharmacol. Drug Dev. 5, 57–68 (2016).

Article

PubMed

Google Scholar

Leto, D. & Saltiel, A. R. Nature Rev. Mol. Cell Biol. 13, 383–396 (2012).

Article

PubMed

Google Scholar

Download references

Related Articles

Read the paper: Dietary cholesterol activates a Ral-dependent pathway driving LDLR turnover

The structure of bad cholesterol comes into focus

Clearing trapped cholesterol could relieve lymphoedema

Subjects

Latest on:

Dietary cholesterol activates a Ral-dependent pathway driving LDLR turnover

Article 24 JUN 26

Freezing brain damage in its tracks: cooling drugs limit stroke injury in mice

News 17 JUN 26

Mitochondria tethered to the nucleus secure its energy supply

News & Views 10 JUN 26

A hidden predictor of sudden cardiac death uncovered by deep learning

News & Views 24 JUN 26

Dietary cholesterol activates a Ral-dependent pathway driving LDLR turnover

Article 24 JUN 26

Freezing brain damage in its tracks: cooling drugs limit stroke injury in mice

News 17 JUN 26

Plant membranes shuffle lipids around to stay firm under heat stress

News & Views 01 JUL 26

Heat-triggered phospholipid flipping stabilizes plasma membrane fluidity

Article 01 JUL 26

Dietary cholesterol activates a Ral-dependent pathway driving LDLR turnover

Article 24 JUN 26