Overview of matrix metalloproteinases (MMPs) in health and disease

Matrix metalloproteinases (MMPs) are a family of structurally related, zinc-dependent endopeptidases with broad substrate specificity, extending far beyond fibrillar collagens to include chemokines, cytokines, growth factors, cell-surface receptors and diverse extracellular matrix (ECM) components. In addition to their well-established proteolytic functions, MMPs can exert non-proteolytic effects through scaffolding roles, interactions with other membrane proteins, or modulation of cell-cell and cell-matrix contacts. Through these catalytic and non-catalytic mechanisms, MMPs influence cell signaling, immunity, barrier function, ECM remodeling, and tissue homeostasis, positioning them as central regulators in both normal physiology and a wide spectrum of acute and chronic diseases. Their dual capacity to either promote tissue repair and resolution or drive inflammation, fibrosis and degeneration, together with the mixed history of broad-spectrum and selective MMP inhibitors in the clinic, has reframed MMPs from simple "matrix-degrading enzymes" to context-dependent, temporally regulated modulators that remain compelling yet challenging therapeutic targets. Importantly, many MMP family members remain poorly characterized in specific tissue, cellular or disease contexts, and for several MMPs, only a limited set of physiological substrates is known or confidently validated in vivo. This book will present contemporary aspects of MMP biology, their context-dependent roles in health and disease, current generations of MMP inhibitors, and both the conceptual and practical challenges, as well as emerging opportunities, in the rational design and development of MMP-targeted therapeutics.