Mucin 4 (MUC4)

Mucin 4 is a very large, membrane-bound glycoprotein encoded by the *MUC4* gene and is part of the transmembrane mucin family. Structurally, it consists of a heavily glycosylated extracellular alpha subunit and a membrane-anchored beta subunit, the latter possessing domains such as EGF-like, NIDO, AMOP, and vWD, which mediate interactions with cell signaling partners (notably ErbB2/HER2). Functionally, Mucin 4 forms part of the mucus barrier on epithelial surfaces, protecting and lubricating tissues in the respiratory tract (trachea, lungs), gastrointestinal tract (esophagus, colon), reproductive system, eyes, and ears. In disease contexts, particularly cancer, MUC4 is often aberrantly upregulated, contributing to tumor cell survival, proliferation, migration, and metastasis by repressing apoptosis, altering cell adhesion, and modulating oncogenic signaling—especially through HER2. MUC4 is extensively investigated both as a biomarker for epithelial cancers and as a potential target for therapeutic intervention, with special interest in its role in resistance to HER2-targeted drugs.

Other names

MUC4Mucin-4Mucin 4, cell surface-associated

Inhibition of MUC4 may suppress interactions with ErbB2/HER2, restoring apoptosis and reducing cell proliferation in cancer. MUC4 may act as a ligand for HER2, stabilizing and potentiating HER2-mediated oncogenic signaling. Drugs targeting HER2 may have reduced efficacy in MUC4-high tumors due to steric hindrance or altered HER2 trafficking.