The determination of the molecular and cellular basis for endocrine and neuroendocrine homeostasis has evolved into an exciting but complex field that provides insight into a staggering array of human diseases. This is in part due to the integration of diverse disciplines ranging from protein structure and enzymology, to protein trafficking, to the genetic analysis of signaling peptide synthesis in endocrine homeostasis. These disciplines are at the heart of the etiology of diseases including diabetes, obesity, cancer and Alzheimer's as well as the physiological basis of drug addiction. The identification of the enzymes--including the proprotein convertases (PCs), select carboxypeptidases, and the a-amidating enzyme --that catalyze the maturation of hundreds of peptide hormones and neuropeptides has been a fundamental step in our understanding of the biosynthesis of signaling peptides and proteins. The study of these enzymes has provided a novel platform to integrate proprotein processing with a variety of cell biological studies, including the regulation of protein traffic and membrane biogenesis, especially Golgi dynamics and sorting, and the formation of dense-core secretory granules in stimulus-coupled endocrine and neuroendocrine cells. Analysis of the PCs has also provided a foundation to study the role of additional membrane-associated proteolytic systems, particularly the matrix metalloproteases and the secretases, that control tissue remodeling and membrane shedding in normal cells, as well as the extracellular activation and/or inactivation of a variety of molecules such as growth factors and antimicrobial peptides. The cooperative roles of the secretory pathway and other protease systems taken in the context of the underlying cellular trafficking machinery that contributes to complex, prevalent diseases such as diabetes, cancer, Alzheimer's disease, and heart disease, provide an urgent reason to bring together these various disciplines in order to examine the interaction of secretory pathway components in disease states. The Proprotein Processing, Trafficking and Secretion Gordon Research Conference is unique in bringing together scientists from a variety of disciplines whose common interest is in the synthesis, trafficking, processing, secretion, and function of signaling peptides and proteins. The purpose of this application is to request financial support for this conference, the only one to integrate and consolidate research from many biological disciplines in order to illuminate the roles of processing enzymes involved in endocrine and CNS homoeostasis and in disease. This conference integrates these areas of study into recent advances in the regulation of protein traffic, the control of secretion and exocytosis from yeast to neurons, and novel genetic and biochemical approaches to the study of peptide diversity.