Unlocking Biology's Potential This session focuses on the unexpected, the mislocalized, and the misunderstood proteins in proteomics. By considering how proteolytic processing, splicing, nonconventional trafficking, and protein-protein interactions lead to new and unexpected roles for protein systems, then the proteomics of tomorrow in the Human Proteome Project today can fill the gap between genomics and phenotypes. Speakers highlight how information is generated in a system that as yet cannot be predicted from the genetic code, protein sequence, or expression data. Rather, proteolytic switching of protein function, pleiotropic roles for moonlighting proteins in unexpected locations, every manner of splicing, and deep protein connections lead to layered information embedded in every proteome. This embellishes the genetic code leading to phenotypic differences between states of a system, between individuals, and between populations of individuals. Such emergent information is ultimately reflected in human health and disease, and in this regard, by unexpected drug off-target effects. Whereas the power of unbiased screens can be lost by biased interpretation, by being open to the unexpected and viewing protein roles as dynamic and interchangeable, then human phenotypes can be mechanistically understood and predictable, human disease has a greater chance of being diagnosed correctly and then treated effectively. Hence, these considerations offer the chance to fill the gap between the genome and phenotypes.