Dpagt1, or dolichyl-phosphate N-acetylglucosaminyltransferase, is an enzyme that catalyzes the first step of protein N-glycosylation, a crucial post-translational modification mechanism. Protein N-glycosylation is essential for many life processes, and Dpagt1 is involved in the biosynthetic pathway of dolichol-linked oligosaccharides required for this process [4].

In mice, Dpagt1 is indispensable for oocyte development. A missense mutation in Dpagt1 causes female subfertility due to defective follicle growth, a thin and fragile zona pellucida in oocytes, and poor developmental competence after fertilization. Conditional knockout of Dpagt1 in oocytes leads to complete infertility, highlighting its importance in female fertility [6]. In human breast cancer, upregulation of DPAGT1 sustains high-level HER2 shedding, conferring trastuzumab resistance. Inhibition of DPAGT1 with tunicamycin acts synergistically with trastuzumab to block HER2 signaling and reverse resistance [1]. Mutations in the human DPAGT1 gene can cause DPAGT1-CDG, characterized by multisystem abnormalities, and is also associated with congenital myasthenic syndrome (CMS) [2,3,4,5,7].

In conclusion, Dpagt1 is essential for protein N-glycosylation and plays a significant role in multiple biological processes such as oocyte development in mice. In human diseases, its dysregulation is associated with breast cancer drug resistance and congenital disorders like DPAGT1-CDG and CMS. Studies on Dpagt1, especially through gene knockout and conditional knockout mouse models, have provided valuable insights into these disease mechanisms.