UBE2C (ubiquitin conjugating enzyme E2 C) is an E2 ubiquitin-conjugating enzyme that catalyzes K11-linked ubiquitin chain assembly and plays critical roles in cell cycle regulation and cancer progression 12. As an essential component of the anaphase promoting complex/cyclosome (APC/C), UBE2C facilitates mitotic exit by promoting degradation of cell cycle proteins through K11-linked polyubiquitination 12. Mechanistically, lactate accumulation during proliferation inhibits SENP1, stabilizing APC4 SUMOylation and enhancing UBE2C binding to APC/C, thereby stimulating timed cell cycle progression 1. In oncogenic contexts, UBE2C is frequently overexpressed and promotes cancer cell proliferation and survival. In lung cancer, UBE2C couples with APC/CDH1 to degrade DEPTOR, activating mTORC signaling and supporting KrasG12D-induced tumorigenesis 2. UBE2C also facilitates cancer metastasis by mediating crosstalk between mono- and polyubiquitination of SNAT2, enhancing glutamine metabolism and VEGFC secretion to promote lymphangiogenesis 3. Additionally, UBE2C expression increases during lung adenocarcinoma invasion and regulates TOP2A stability, affecting doxorubicin sensitivity in breast cancer 45. These findings establish UBE2C as both a cell cycle regulator and oncogenic driver with therapeutic potential.