The development of compartments in eukaryotic cells and the distribution of nuclear-encoded proteins underlies the specialization of cellular functions. The exploration of the proteome of the cell in terms of the collection of its subcompartments is therefore both a practical approach and also a function led necessity that recognizes that proper interpretation of proteomic data requires information about compartmentation of protein machinery.

Subcellular proteomics decreases the complexity of proteomie discovery. With the typical compartment representing 500-4000 proteins, its analysis by gel based and MS based systems approach the resolution of the analytical techniques. In contrast, whole cell proteomes of 12,000-40,000 proteins extend well beyond the ability of proteomic tools to resolve them, leaving whole cell proteome studies being “tip of the iceberg” activities. Subcellular proteomics stands on the shoulders of decades of biochemical research that has developed methods for isolation of subcellular compartments. Extensive laboratory work involving the tinkering with density, size, and charge separation techniques has enabled incremental limitation of contamination in isolation methods from a range of subcellular structures.