Advances in peptidomics: analytical strategies and biological insights for clinical applications.

INTRODUCTION

Endogenous peptides are emerging as key regulators of physiological and pathological processes and represent promising biomarkers and therapeutic targets. Advances in peptidomics have substantially improved their discovery and characterization, providing new insights into peptide biogenesis, biological functions, and clinical applications. This review summarizes current knowledge on endogenous peptide generation, analytical workflows, biological functions, and emerging diagnostic and therapeutic applications. A literature search was conducted using PubMed, Scopus, and Web of Science, focusing primarily on studies published between 2020 and 2026.

AREAS COVERED: This review: (1) examines MS-based analytical strategies for peptidome characterization; (2) highlights major peptidomics subfields, including immunopeptidomics, neuropeptidomics, degradomics, fragmentomics, and secretomics; (3) discusses current biological and clinical applications, with emphasis on biomarker discovery, disease monitoring, and theranostic development in oncology, neurodegenerative, metabolic, reproductive, and infectious diseases. The review also summarizes current advances in liquid biopsy peptidomics.

EXPERT OPINION: Peptidomics is evolving from a discovery-driven discipline into a clinically relevant platform for biomarker identification and therapeutic development. Future progress will depend on standardized workflows, advanced MS technologies, AI-supported data analysis, and multi-omics integration to enable robust clinical translation and precision medicine.