MAN2A1 (mannosidase alpha class 2A member 1) is a Golgi-localized enzyme that catalyzes the conversion of high-mannose to complex N-glycans, representing a critical step in N-glycan maturation 1. The enzyme controls the final hydrolytic step in N-glycan processing and is involved in viral protein processing [GO annotations]. Beyond its canonical glycosylation function, MAN2A1 has emerged as a significant factor in human malignancy and neuropsychiatric disease. A MAN2A1-FER fusion protein, expressed in multiple tumor types including hepatocellular carcinoma, non-small cell lung cancer, ovarian and prostate tumors, exhibits constitutively elevated tyrosine kinase activity and promotes cancer cell proliferation, invasion, and metastasis through EGFR-BRAF-MEK-AKT pathway activation 2. Conversely, MAN2A1 inhibition enhances anti-tumor immunity by increasing cancer cell sensitivity to T-cell-mediated killing and synergizes with anti-PD-L1 immunotherapy in preclinical models 1. Genetically, MAN2A1 variants are associated with schizophrenia susceptibility, suggesting altered glycosylation patterns affect neurotransmitter receptor function and brain development 3. MAN2A1 mutations also correlate with rectal neuroendocrine neoplasm progression and lymph node metastasis 4. These findings underscore MAN2A1's dual role in N-glycan biosynthesis and oncogenic signaling, with therapeutic potential as both a kinase inhibitor target and immunomodulatory intervention point.