In the past decade, the notion has evolved that lipids are not just structural insulators that separate intracellular and extracellular spaces, but that they can also function as versatile signalling molecules.

Rather than functioning as passive insulators, cellular membranes along the secretory pathway are very dynamic and have constantly changing lipid composition. Cholesterol, for example, is trafficked to specific tissues using different transport pathways and these regulatory mechanisms help maintain cholesterol compartmentalization and homeostasis. Among the most well known lipid signalling molecules are inositol derivatives, which have varied distributions and functions across the three kingdoms of life. Sphingolipids are another group of signalling lipids with important roles in regulating the cell cycle, stress responses, pro-inflammatory pathways and cell migration. It has become evident in recent years that distortions in lipid signalling networks are at the heart of many diseases, such as metabolic disease, cancer, inflammation and neurodegeneration. The pharmacological modulation of lipid-dependent signalling pathways should promote synergistic targeting approaches with improved therapeutic opportunities. Finally, the association of proteins with the surface of intracellular membranes is critical for a wide variety of cellular functions — from signalling and trafficking to cell structure — and employs an ever-growing array of lipid-binding domains. All of these topics, and more, are represented in this Focus, which is part of the February 2008 issue of Nature Reviews Molecular Cell Biology, providing a snapshot of lipid biology.

Accompanying this Focus is a Poster 'Targeting lipid signalling in disease', which was produced with support from Merck Serono International S.A.