The brain is composed of approximately 60% to 70% lipids, which primarily serve as structural components. However, many of these lipids also play critical roles in cellular signaling. In particular, sphingolipids and lysophospholipids function as second messengers, direct receptor ligands, and/or metabolic intermediates in various signaling pathways. Intracellularly, lysophospholipids serve as intermediate precursors for the biosynthesis of other lipids, whereas extracellular lysophospholipids act as signaling molecules that mediate diverse physiological processes. Dysregulation of sphingolipid and lysophospholipid metabolism has been increasingly associated with the pathogenesis of neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis, suggesting that lipid signaling plays a pivotal role in neuroinflammation, synaptic dysfunction, and neuronal survival.

Despite extensive research, the underlying mechanisms of neurodegenerative disorders remain incompletely understood. Emerging evidence highlights a critical role for bioactive lipids—particularly sphingolipids and lysophospholipids—in modulating neuroinflammation, membrane dynamics, and neuronal survival. Dysregulation of lipid signaling has been increasingly associated with the pathogenesis of disorders such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. Recent advances in lipidomics, single-cell transcriptomics, and high-resolution imaging now enable a more detailed understanding of lipid metabolism in the nervous system. This Research Topic aims to compile original research and reviews focused on lipid signaling in neurodegeneration. Gaining insight into these pathways may not only deepen our understanding of neurodegenerative disease mechanisms but also lead to the identification of novel diagnostic biomarkers and therapeutic targets.

Specific themes include, but are not limited to:

• Lipidomics profiling in neurological conditions

• Molecular mechanisms linking lipid dysregulation to neurodegeneration and neuroinflammation

• Lipid–glia–neuron interactions

• Lipid-based biomarkers for early diagnosis and disease monitoring

• Therapeutic targeting of lipid signaling pathways

• Animal or cellular models of lipid-mediated neurodegeneration

• Impact of lipid metabolism on autophagy, mitochondrial function, or membrane dynamics

We invite the submission of Original Research articles, Reviews, Mini-Reviews, Perspectives, and Method articles. Both basic and translational studies are encouraged. Contributions combining multi-omics approaches, innovative imaging techniques, or novel experimental models are particularly welcome.

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Lipid Signaling in Neurological Disorders: From Neurodegeneration to Neuroinflammation