So much of the cool stuff in proteomics, particularly when we're dealing with drug and stress response relies on events occurring at the cell surface with signals transmitted through to the cytoplasm. Membrane proteomics is no easy task. The proteins have big hydrophobic regions that are hard to separate from the membrane chunk and sometimes even more difficult to digest and ionize.
If you are interested in this topic:
There have been tons of reviews on this topic (including my humble attempt to sum up membrane phosphoproteomics..insert shameless plug!). This new one in press at MCP from Xi Zhang is a whole lot better and much more up-to-date and is a stellar review for someone interested in this topic and the cutting edge technologies.
Notably, Dr. Zhang's review never mentions one of the classic (and still maybe one of the best!) solvent digestion methods pioneered by Josip Blonder and Dick Smith. If you're going into getting a ton of membrane coverage, I think it would be a mistake to forget about this one!