MAN1C1 (mannosidase alpha class 1C member 1) is a Golgi-localized enzyme that catalyzes the trimming of alpha-1,2-linked mannose residues from N-linked oligosaccharides, converting Man(9)GlcNAc(2) to Man(8)GlcNAc(2) and subsequently to Man(6)GlcNAc(2), a critical step in N-glycan maturation 1. This glycosylation function plays context-dependent roles in disease: MAN1C1 acts as a tumor suppressor in clear cell renal cell carcinoma, where its re-expression induces apoptosis and inhibits epithelial-mesenchymal transition 2. Conversely, MAN1C1 loss promotes intrahepatic cholangiocarcinoma tumorigenesis by generating alpha-1,2-mannosylated CD133 that enhances CD133-FIP200 interaction in tumor-initiating cells 3. In glioblastoma, elevated MAN1C1 associates with poor prognosis and immunological dysfunction in the tumor microenvironment, suggesting an oncogenic role in glioma stem cells 4. Proteome-wide Mendelian randomization identified MAN1C1 as a protein whose genetically predicted lower circulating levels increase ovarian cancer risk 5. Additionally, MAN1C1 coordinates CD147 clustering during epithelial cell migration through mannose-trimming activity 6. These findings indicate MAN1C1 functions as a context-dependent regulator of glycosylation with distinct implications across cancer types.