In an Advanced Online Publication from Nature Genetics, Klose at al. describe a comprehensive genetic study of proteins in mice brains (25 March 2002, DOI:10.1038/ng861). They took advantage of crosses from the European collaborative interspecific backcross (EUCIB) project, and prepared brain tissues from 200 backcross progeny (B1) animals. They then analyzed the brain proteome using two-dimensional gel electrophoresis. Comparison of over 8000 gel spots from two distantly related mouse strains (Mus musculus C57BL/6 and Mus spretus SPR) led to the identification of over 1000 polymorphic proteins that differed either qualitatively or quantitatively. Klose at al. then mapped the genetic loci corresponding to hundreds of these protein variants. Quantitative differences were often associated with allele-specific variation, but additional loci also contributed to protein polymorphisms, emphasising the importance of polygenic modifier effects.