Serglycin Across the Disease Spectrum: A Multifunctional Proteoglycan in Inflammation and Cancer

The inflammatory response possesses a central role in human pathophysiology, regulating the tissue microenvironment and cell signaling. Inflammation occurs either as a symptom of homeostasis disturbance or as a driver for determining cell fate. In this context, cells recruit secreted cytokines, chemokines and intracellular mediators, in cooperation with their surrounding cellular components, to integrate inflammatory stimuli. The extracellular matrix (ECM) acts as a scaffold for shaping tissue structure and simultaneously undergoes continuous remodeling to provide a dynamic network for intercellular communication. Serglycin (SRGN) is the only known intracellular and extracellular proteoglycan, implicated in the formation of secretory vesicles and ECM reorganization. The regulatory roles of SRGN in the bioavailability of secreted factors, as well as SRGN pleiotropic interactions within the ECM, as well as with cell surface receptors, have emerged to beessential for inflammatory diseases and tumor progression. Its overexpression and excessive secretion, alongside its contribution to cell signaling, highlight the potential diagnostic and therapeutic aspects of SRGN in human diseases.