Abstract. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that are collectively capable of cleaving virtually all extracellular matrix (ecM) substrates and play an important role in diverse physiological and pathological processes. The activity of MMPs is controlled at multiple levels, and the transcriptional regulation of MMPs appears to represent a necessary step in its regulation. MMP-3 is a key member of the MMP family with broad substrate specificity, and is crucial to the connective tissue remodeling process. it is also involved in the turnover of the numerous ecM components. a common functional promoter polymorphism of MMP-3, 5a/6a, affects its activity and has been associated with various diseases. This polymorphism may be used as a genetic marker for certain pathologies to identify individual susceptibility. This review discusses various topics related to MMP-3 in pathological processes, with a focus on the 5a/6a polymorphism. Contents1. introduction 2. Matrix metalloproteinase-3 3. 5a/6a polymorphism of MMP-3 4. Pathological processes and the MMP-3 5a/6a polymorphism 5. Haplotype influence IntroductionThe evidence that individual characteristics play an important role in physiological and pathological processes has resulted in the targeted study of genetic polymorphisms in the clinical setting. in this context, mediators that degrade the extracellular matrix (ecM), such as matrix metalloproteinases (MMPs), are highlighted in studies involving inflammatory and degenerative diseases, and principally the prognosis and metastasis of cancer.degradation of the ecM is essential in many physiological processes, such as during development, growth and repair of tissue, and the microenvironment plays a central role in controlling both normal and transformed cell functions, as well as normal tissue integrity (1).MMPs are a pivotal family of zinc enzymes responsible for the degradation of ecM components, including basement membrane collagen, interstitial collagen, fibronectin and various proteoglycans, during normal remodeling and repair processes in development and inflammation. MMPs are also peptidase enzymes responsible for clotting factors, lipoproteins, latent growth factors and chemotactic and cell adhesion molecules (2,3). in this way, MMPs play a key role in the physiologic remodeling of tissues, including embryogenesis and tissue morphogenesis, angiogenesis, cell migration, proliferation, apoptosis, alteration of cell motility, effects on the immune system, wound repair and the inflammatory response (4).MMPs are a family of more than 25 enzymes. The expression of most MMPs is normally low in tissues and is induced when remodeling of the ecM is required. MMP gene expression is regulated primarily at the transcriptional level, but there is also evidence of the modulation of mrna stability in response to growth factors and cytokines (5). The promoter region of inducible MMP genes (i.e., MMP-3) shows remarkable conservation of regulatory elements, and their expression is induced ...