Dysregulation of lipid metabolism plays a major role in the aetiology and sequelae of inflammatory disorders, cardiometabolic and neurological diseases, and several forms of cancer. Recent advances in lipidomic methodology allow comprehensive lipidomic profiling of clinically relevant biological samples, enabling researchers to associate lipid species and metabolic pathways with disease onset and progression. The resulting data serve not only to advance our fundamental knowledge of the underlying disease process, but also to develop risk assessment models to assist in the diagnosis and management of disease. Currently, clinical applications of in-depth lipidomic profiling are largely limited to the use of research-based protocols in the analysis of clinical trial sample sets. However, we foresee the development of purpose-built clinical platforms designed for continuous operation and clinical integration - assisting healthcare providers with disease risk assessment, diagnosis, and monitoring. Herein, we review the current state of clinical lipidomics and the techniques employed in lipidomic profiling, with a primary focus on mass spectrometry-based analysis. We discuss the prospective design of clinically integrated platforms, including practical considerations for sample collection, storage, and preparation; automation solutions for high-throughput analysis; available software packages, and statistical development of risk assessment models.

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