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SMAD4 family member 4, also known as SMAD4, is a protein that in human is encoded by the SMAD4 gene. It is often found mutated in many cancers. It acts as a tumor suppressor that functions in the regulation of the TGF-β signal transduction pathway, which negatively regulates growth of epithelial cells and the extracellular matrix (ECM). SMAD4 alterations have been found in multiploid colorectal cancer and pancreatic carcinoma. It is found inactivated in at least 50% of pancreatic cancers. It is also found mutated in the autosomal dominant disease juvenile polyposis syndrome (JPS).