Niphakis, M.J. et al. Cell 161, 1668–1680 (2015).

Lipids interact with proteins in the cell and play important roles in regulating protein function. Niphakis et al. investigated these interactions on a global scale, generating a map of the human lipid-binding proteome. To create this map, they developed a set of common fatty acid–based chemical probes that allowed them to enrich for lipid-binding proteins, which they then identified using quantitative mass spectrometry. Using arachidonoyl lipid probes, they identified more than 1,000 lipid-binding proteins in HEK293T and Neuro2a cells. They also used the lipid probes in a competitive ligand screen to identify small-molecule compounds selective for the protein nucleobindin 1. Both the lipid-based probes and the lipid-binding proteome map should be useful for understanding the role of lipids in regulating protein function and for identifying small-molecule drugs and chemical probes.