IBN-9507952 Nillni, Eduardo A. Thyrotropin-releasing hormone (TRH) is a peptide of great biological interest because of its diverse functions within the central nervous system ranging from a critical role in regulating endocrine function to modulating behavior. TRH is synthesized as a large precursor molecule containing multiple copies of the peptide. A lingering question has been how this precursor molecule is processed to yield mature TRH within the central nervous system. Previously, Dr. Eduardo Nillni and his laboratory have made significant contributions to our understanding of precursor processing. In the present work, he will continue to examine the role of subcellular organelles in processing of the TRH precursor and the role of several compartment specific enzymes in the processing. In addition, these studies have the potential to significant new information about differential processing of the two ends of the precursor molecule and the mechanisms regulating this differential processing. The studies proposed by Dr. Nillni form the basis for understanding the mechanisms the brain and other organs use for generating the messenger molecules the cells of the body use to communicate with one another. Aberrations in these normal cellular processes may have serious consequences for human health and disease.