The extracellular matrix (ECM) is a dynamic structure present in all tissues, continuously undergoing controlled remodeling to regulate tissue homeostasis and organ development. This process involves quantitative and qualitative changes in the ECM, mediated by specific enzymes such as metalloproteinases (MMPs). The ECM interacts with cells to regulate functions like proliferation, migration, and differentiation. Dysregulation of ECM composition, structure, stiffness, and abundance contributes to pathological conditions such as fibrosis and invasive cancer. Understanding how the ECM regulates organ structure and function and how ECM remodeling affects disease progression is crucial for developing new therapeutics. The ECM is composed of around 300 proteins, including collagen, proteoglycans, and glycoproteins. These components play essential roles in tissue integrity, hydration, and signaling. ECM breakdown is primarily mediated by MMPs, ADAMs, and other proteases, which can also release biologically active molecules. The ECM dynamics in intestinal development, branching morphogenesis, and disease progression are discussed, highlighting the importance of ECM remodeling in these processes. Aberrant ECM remodeling can lead to tissue destruction, fibrosis, and cancer. Therapeutic strategies targeting the ECM and its remodeling enzymes offer promising opportunities for treating various diseases.The extracellular matrix (ECM) is a dynamic structure present in all tissues, continuously undergoing controlled remodeling to regulate tissue homeostasis and organ development. This process involves quantitative and qualitative changes in the ECM, mediated by specific enzymes such as metalloproteinases (MMPs). The ECM interacts with cells to regulate functions like proliferation, migration, and differentiation. Dysregulation of ECM composition, structure, stiffness, and abundance contributes to pathological conditions such as fibrosis and invasive cancer. Understanding how the ECM regulates organ structure and function and how ECM remodeling affects disease progression is crucial for developing new therapeutics. The ECM is composed of around 300 proteins, including collagen, proteoglycans, and glycoproteins. These components play essential roles in tissue integrity, hydration, and signaling. ECM breakdown is primarily mediated by MMPs, ADAMs, and other proteases, which can also release biologically active molecules. The ECM dynamics in intestinal development, branching morphogenesis, and disease progression are discussed, highlighting the importance of ECM remodeling in these processes. Aberrant ECM remodeling can lead to tissue destruction, fibrosis, and cancer. Therapeutic strategies targeting the ECM and its remodeling enzymes offer promising opportunities for treating various diseases.