UBE2I encodes the sole E2 SUMO-conjugating enzyme essential for protein SUMOylation, a critical post-translational modification. UBE2I accepts SUMO proteins from E1 enzymes and catalyzes their covalent attachment to target proteins with E3 ligases, enabling formation of poly-SUMO chains 1. The protein is ubiquitously expressed and maps to chromosome 16.3, showing homology to yeast UBC9 which is critical for cell cycle progression 1. UBE2I plays essential roles in maintaining epigenetic gene silencing, as demonstrated by genome-wide screening identifying it among key factors required for this process 2. In cancer contexts, UBE2I exhibits complex functions: it promotes tumorigenesis in ovarian, thyroid, and cervical cancers through mechanisms involving immune modulation and cellular localization changes 345. Specifically, UBE2I regulates macrophage polarization toward M1 phenotype and enhances immunotherapy efficacy in ovarian cancer 3, while promoting hnRNPA2B1 cytoplasmic localization in thyroid cancer 4. Additionally, UBE2I controls p27kip1 nuclear export in cholangiocarcinoma, affecting chemosensitivity 6. In metabolic regulation, adipocyte-specific UBE2I deletion causes severe lipoatrophy and metabolic dysfunction, indicating its requirement for proper adipose tissue expansion 7.