We study the cell biology of endocrine and neuroendocrine cells, focusing on the mechanisms of biosynthesis and intracellular trafficking of peptide hormones and neuropeptides and their processing enzymes, the regulation of dense-core secretory granule biogenesis, and the physiological roles of the prohormone processing enzyme carboxypeptidase E. We discovered novel molecular mechanisms of protein trafficking to the regulated secretory pathway and identified players and mechanisms that control secretory granule biogenesis and transport in endocrine and neuroendocrine cells and neurons. Using cell lines, primary cell cultures, and mouse models, we have gained a better understanding of diseases related to defects in hormone and neuropeptide targeting, synaptic transmission, memory, and learning and of diabetes and obesity. Recently, we discovered a splice isoform of carboxypeptidase E (CPE-ΔN) that is highly expressed in metastatic tumor cells. We are investigating the mechanism by which CPE-∆N promotes tumor growth and metastasis as well as the use of CPE-∆N as a biomarker for metastatic potential of primary tumors and a therapeutic target for malignant tumors. Studies in human tumor cell lines, primary and metastatic tumors, and mouse models have provided new insights into the mechanism of tumor metastasis, facilitating the identification of a potential therapeutic target for suppressing tumor metastasis.