More than two decades have passed since the discovery of the first SLRP decorin, and to date eighteen members of this protein family have been identified, many of which are now recognised as potential biomarkers of extracellular matrix dysregulation. SLRPs plays significant role as an initiator, a link protein molecule, and an inhibitor of various types of signaling pathway in diverse range of pathophysiological disease processes involving a spectrum of biological actions, such as host defense, regulation of gene expression, cellular homeostasis, wound healing, inflammation, autoimmunity, oncogenesis, and collagen fibrillogenesis. SLRPs as a signaling molecule mediate interactions with various growth factors, cell receptors, matrix-degrading enzymes, and many other matrix components involved in cell growth, morphogenesis, cell death, and immunity. SLRPs and their fragmented peptides can alter signaling pathways thorough affinity-based interactions within cell and tissue, involving specific tyrosine kinase and Toll-like receptors, underscoring their critical roles as damage-associated molecular patterns (DAMPs). This chapter presents a conclusive overview on the multifunctional role of SLRPs highlighting their potential recognition as DAMP, by the host immune system across various tissue types. This presented perspective thus aims to rationalize the impact of SLRP function as a key mediator of inflammatory signaling process.