Proteomics has revealed that many proteins are present in unexpected cellular locations. Moreover, it is increasingly recognized that proteins can translocate between intracellular and extracellular compartments in non-conventional ways. This increases gene pleiotrophy as the diverse functions of the protein that the gene encodes are dependent on the cellular location. Given that trafficking drug targets may exist in various forms--often with completely different functions--in multiple cellular compartments, careful interpretation of proteomics data is needed for an accurate understanding of gene function. This Perspective is intended to inspire the investigation of unusual protein localizations, rather than assuming that they are due to mislocalization or artefacts. Given a fair chance, proteomics could reveal novel and unforeseen biology with important ramifications for target validation in drug discovery.