MUC proteins have great significance as prognostic and diagnostic markers as well as a potential target for therapeutic interventions in most cancers of glandular epithelial origin. These are high molecular weight glycosylated proteins located in the epithelial lining of several tissues and ducts. Mucins belong to a heterogeneous group of large O-glycoproteins that can be either secreted or membrane-bound. Glycosylation, a post-translational modification affects the biophysical, functional and biochemical properties and provides structural complexity for these proteins. Aberrant expression and glycosylation of mucins contribute to tumour survival and proliferation in many cancers, which in turn activates numerous signalling pathways such as NF-kB, ERα, HIF, MAPK, p53, c-Src, Wnt and JAK-STAT, etc. This subsequently induces cancer cell growth, proliferation and metastasis. The present review mainly demonstrates the functional aspects of MUC glycoproteins along with its unique signalling mechanism and role of aberrant glycosylation in cancer progression and therapeutics. The importance of MUC proteins and its subtypes in a wide spectrum of cancers including but not limited to breast cancer, colorectal cancer, endometrial and cervical cancer, lung cancer, primary liver cancer, pancreatic cancer, prostate cancer and ovarian cancer has been exemplified with significance in targeting the same. Several patents associated with the MUC proteins in the field of cancer therapy are also emphasized in the current review.