Mucin-4 (MUC-4) is a mucin protein that in humans is encoded by the MUC4 gene. Like other mucins, MUC-4 is a high-molecular weight glycoprotein. The major constituents of mucus, the viscous secretion that covers epithelial surfaces such as those in the trachea, colon, and cervix, are highly glycosylated proteins called mucins. These glycoproteins play important roles in the protection of the epithelial cells and have been implicated in epithelial renewal and differentiation. This gene encodes an integral membrane glycoprotein found on the cell surface, although secreted isoforms may exist. At least two dozen transcript variants of this gene have been found, although for many of them the full-length transcript has not been determined or they are found only in tumor tissues. MUC-4 has been found to play various roles in the progression of cancer, particularly due to its signaling and anti-adhesive properties which contribute to tumor development and metastasis. It is also found to play roles in other diseases such as endometriosis and inflammatory bowel disease. MUC-4 belongs to the human mucin family that is membrane-anchored and can range in molecular weight from 550 to 930 kDa for the actual protein, and up to 4,650 kDa with glycosylation. Structure MUC4 is an O-glycoprotein that can reach up to 2 micrometers outside the cell. MUC4 mucin consists of a large extracellular alpha subunit that is heavily glycosylated and a beta subunit that is anchored in the cell membrane and extends into the cytosol. This beta subunit is considered an oncogene, whose role in cancer is increasingly being recognized particularly due to its involvement in signalling pathways, particularly with ErbB2 (Her2). This subunit serves as a ligand for ErbB2, which is suggested to cause the repression of apoptosis found in many cancer cells. The large alpha subunit that is glycosylated likely confers the anti-adhesive properties to the cell, allowing for cell–cell and cell–matrix detachment in normal as well as cancerous cells. The heavy glycosylation may also serve as a reservoir for growth factors, which may become released upon degradation. The two subunits of MUC4 are transcribed from a single gene made of 25 exons and with its exon/intron structure identical to that of the mouse gene. Over 24 splice variants have been found for MUC4 using commercial mRNAs or total RNAs extracted from cancer cell lines. Some predicted forms are soluble, while others are membrane bound. However, most of these splice variants