Signaling lipids: An overview of emerging physiological functions

Abstract

Lipids are now recognized as central regulators of cellular signaling, extending well beyond their traditional roles in membrane structure and energy storage. As spatially confined and rapidly inducible messengers, signaling lipids integrate membrane dynamics, metabolism, and signal transduction to control processes like inflammation, immune responses, vesicular trafficking, cytoskeletal organization, and cell fate decisions. This review highlights key mechanistic principles underlying lipid signaling specificity, including localized biosynthesis, enzymatic turnover, and receptor engagement. We trace the evolution of the field from classical eicosanoids and phosphoinositides to sphingolipids, lysophospholipids, and endocannabinoids, and focus on emerging mediators such as fatty acid esters of hydroxy fatty acids, specialized pro-resolving mediators, and lysophosphatidylserines. We conclude by discussing how dysregulated lipid signaling contributes to disease and outline future directions, emphasizing membrane contact sites, signaling crosstalk, and advances in lipidomics and imaging.