Understanding peptide hormones: from precursor proteins to bioactive molecules

Peptide hormones are fundamental regulators of biological processes involved in homeostasis regulation and are often dysregulated in endocrine diseases. Despite their biological significance and established therapeutic potential, there is still a gap in our knowledge of their processing and post-translational modifications, as well as in the technologies for their discovery and detection. In this review, we cover insights into the peptidome landscape, including the proteolytic processing and post-translational modifications of peptide hormones. Understanding the full landscape of peptide hormones and their modifications could provide insights into leveraging proteolytic mechanisms to identify novel peptides with therapeutic potential. Therefore, we also discuss the need for future research aiming at better predicting, detecting, and characterizing new peptides with biological activities.