Small Leucine Rich Proteoglycans: Decorin Still at the Crossroads of Extracellular Matrix Homeostasis, Fibrosis, and Cancer

Small leucine-rich proteoglycans (SLRPs) are an important group of molecules in the extracellular matrix (ECM) that are involved in regulating collagen assembly, tissue homeostasis, and cell signalling pathways. Among them, Decorin represents the proto-type member and plays a central role in maintaining ECM integrity, regulating fibrosis, and controlling tumor progression. This review examines the structural and functional biology of SLRPs, with a special focus on Decorin, highlighting its involvement in fibrotic diseases, degenerative disorders and the tumor microenvironment. Decorin acts as a multifunctional regulator through its interactions with TGF-β, various tyrosine kinase receptors, and multiple ECM components, carrying out anti-fibrotic, anti-angiogenic, anti-cancer, and tumour-suppressive functions. Additionally, factors such as the contribution of SLRPs to the desmoplastic response of tumors, their potential use as biomarkers for extracellular matrix remodelling, and the emerging therapeutic prospects based on administering recombinant Decorin, gene therapies, mimetic molecules, and strategies targeting the ECM. Overall, SLRPs, especially Decorin, stand out as key molecules in integrating structural and molecular signals and as promising diagnostic and therapeutic targets in fibrotic and neoplastic diseases.