Phospholipase D Signaling in Disease Mechanisms
Summary
Phospholipase D (PLD) enzymes catalyse the hydrolysis of membrane phospholipids, primarily phosphatidylcholine, to generate phosphatidic acid (PA), a versatile lipid second messenger. Two classical mammalian isoforms, PLD1 and PLD2, are regulated by small GTPases, protein kinase C and lipid cofactors, allowing tight control over their subcellular localisation and activity. PA modulates membrane curvature, recruits effector proteins and orchestrates key signalling cascades such as PI3K/Akt, mTOR and MAPK, thereby governing processes from vesicle trafficking and cytoskeletal dynamics to cell survival and proliferation. Dysregulated PLD signalling has been implicated in a spectrum of diseases: in oncology, elevated PLD activity supports tumour growth, invasion, metastasis and chemoresistance; in inflammation, PLD-derived PA fosters cytokine release and leukocyte recruitment; in neurodegeneration, altered PA homeostasis disrupts synaptic function and membrane trafficking; and in microbial pathogenesis, bacterial PLD orthologues contribute to host invasion and toxin delivery. The global significance of PLD research lies in its potential to inform novel therapeutic strategies, including isoform-selective inhibitors, lipid-based interventions and precision optogenetic tools, thereby addressing critical unmet needs in cancer, immune disorders and neurological disease.
Research from Nature Portfolio
No recent Nature Portfolio content available.
Phospholipase D Signaling in Disease Mechanisms publication trend
The graph below shows the total number of articles in phospholipase d signaling in disease mechanisms across all publications each year (not limited to Nature Index journals).
Technical terms
Phospholipase D (PLD): A family of enzymes that hydrolyse membrane phospholipids to generate phosphatidic acid.
Phosphatidic acid (PA): A bioactive lipid second messenger that regulates membrane curvature and signal transduction.
Chemoresistance: The capacity of cancer cells to withstand the cytotoxic effects of chemotherapeutic agents.
Optogenetics: A technique that employs light-sensitive protein domains to control cellular processes with high spatial and temporal resolution.
References
- Thematic Review Series: Phospholipases: Central Role in Lipid Signaling and Disease. Journal of Lipid Research (2015).
- PLD1 is a key player in cancer stemness and chemoresistance: Therapeutic targeting of cross-talk between the PI3K/Akt and Wnt/β-catenin pathways. Experimental & Molecular Medicine (2024).
- Ultralow Background Membrane Editors for Spatiotemporal Control of Phosphatidic Acid Metabolism and Signaling. ACS Central Science (2024).
- Phosphatidic Acid: From Pleiotropic Functions to Neuronal Pathology. Frontiers in Cellular Neuroscience (2019).
- Phospholipase D (PLD) drives cell invasion, tumor growth and metastasis in a human breast cancer xenograph model. Oncogene (2013).
- Functional Regulation of Phospholipase D Expression in Cancer and Inflammation*. Journal of Biological Chemistry (2014).
- Deficiencies of the Lipid-Signaling Enzymes Phospholipase D1 and D2 Alter Cytoskeletal Organization, Macrophage Phagocytosis, and Cytokine-Stimulated Neutrophil Recruitment. PLOS ONE (2013).
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.