Mevalonate Pathway Disorders and Inflammatory Syndromes
Summary
The mevalonate pathway is a central metabolic cascade responsible for the synthesis of cholesterol and a broad array of non-sterol isoprenoids. Genetic defects affecting key enzymes such as mevalonate kinase (MVK) or phosphomevalonate kinase (PMVK) disrupt the production of critical lipid intermediates, leading to a spectrum of autoinflammatory syndromes. Clinical manifestations range from recurrent febrile episodes, arthralgia and mucocutaneous lesions to severe presentations that include cytopenias, neurodevelopmental delay and organ dysfunction. At the molecular level, deficiency of isoprenoid end-products impairs protein prenylation, disturbs mitochondrial homeostasis and primes inflammasome activation, with consequent overproduction of interleukin-1β and interleukin-18. Recent advances have clarified the genetic heterogeneity of these conditions and highlighted the central role of innate immune dysregulation. Therapeutic strategies now encompass targeted cytokine blockade, modulation of inflammasome assembly and, in experimental settings, supplementation with exogenous isoprenoid compounds. These developments underscore the global significance of mevalonate pathway research for the diagnosis, management and potential prevention of debilitating systemic inflammatory diseases.
Research from Nature Portfolio
No recent Nature Portfolio content available.
Mevalonate Pathway Disorders and Inflammatory Syndromes publication trend
The graph below shows the total number of articles in mevalonate pathway disorders and inflammatory syndromes across all publications each year (not limited to Nature Index journals).
Technical terms
Mevalonate pathway: A sequence of enzymatic reactions generating cholesterol and isoprenoid intermediates essential for cellular functions.
Isoprenoids: Lipid-derived molecules produced by the mevalonate pathway that serve as precursors for sterols and lipid modifications of proteins.
Protein prenylation: A post-translational process in which isoprenoid groups attach to proteins, facilitating membrane association and signal transduction.
Autoinflammatory syndrome: A group of disorders characterised by innate immune dysregulation leading to recurrent sterile inflammation.
Inflammasome: A cytosolic multiprotein complex that activates caspase-1, promoting maturation and secretion of interleukin-1β and interleukin-18.
References
- Phosphomevalonate kinase deficiency expands the genetic spectrum of systemic autoinflammatory diseases. Journal of Allergy and Clinical Immunology (2023).
- Mevalonate kinase deficiency: an updated clinical overview and revision of the SHARE recommendations. Frontiers in Immunology (2024).
- Mevalonate Pathway Blockade, Mitochondrial Dysfunction and Autophagy: A Possible Link. International Journal of Molecular Sciences (2015).
- Block of the Mevalonate Pathway Triggers Oxidative and Inflammatory Molecular Mechanisms Modulated by Exogenous Isoprenoid Compounds. International Journal of Molecular Sciences (2014).
- Compromised Protein Prenylation as Pathogenic Mechanism in Mevalonate Kinase Deficiency. Frontiers in Immunology (2021).
About these summaries
This Nature Research Intelligence Topic summary is created with the cited references and a large language model. We take care to ground generated text with facts, and have systems in place to gain human feedback on the overall quality of the process in line with our AI principles. We strive to create accurate and useful summaries for people unfamiliar with the research topic and that supports this goal. These pages are a beta release and will be updated as we learn how best to help people gain value from a research topic summary.
Turn complex research questions into confident strategic decisions
When you're under pressure to set direction, justify investment, or understand your competitive position, you need more than raw data — you need trusted insights you can act on.
Benchmark your performance against global peers using robust, methodologically sound analysis.
Combine quantitative metrics with qualitative expert insight to uncover strengths, gaps and emerging opportunities.
Gain tailored, decision-ready recommendations aligned to your strategic priorities.
Talk to us to learn more about our data dashboards and bespoke strategy reports.
Grow research skills, confidence and careers with training built for every stage of the research lifecycle.
Developed with Nature Portfolio journal Editors and internationally renowned experts. Discover three ways to learn:
Self-paced, online courses in convenient bite-sized units, covering key skills across scientific writing, publishing, grant writing, data analysis, and more.
Expert trainer-led workshops with hands-on exercises and real-time feedback across core research skills, delivered via interactive group sessions.
Editor-led workshops combining core principles in writing and publishing, personalised 1:1 feedback from Nature Portfolio Editors and hands-on exercises.
Explore course catalogues and workshop agendas, enquire about the options or request institutional pricing.