The ins and outs of lipid domain proteomics

Lipid domains, also known as lipid rafts, are segregated from the bulk of the plasma membrane and have been attributed a multitude of important cellular functions in both health and disease. The large number of recent proteomic studies of their composition has produced a stunning list of potential constituents, leading to many contradictory conclusions. The actual methodology used in the different studies therefore seems to be of pivotal importance with regard to the derived lipid domain proteomes. In this review, we attempt to interpret recent findings in light of the methodology used and identify potential artifacts. This integrative view tries to tentatively define the core composition, the associated functions, the topology, as well as the dynamics of lipid domain proteomes. In other words: who's in and who's out.