CUEDC2 (CUE domain containing 2) is a multifunctional protein with primary roles in protein degradation, cell cycle regulation, and inflammatory control. Its canonical function involves downregulating estrogen receptor-α (ERα) and progesterone receptor through ubiquitin-proteasome-mediated degradation, independent of hormone presence 1. CUEDC2 is phosphorylated by Cdk1 during mitosis, promoting anaphase-promoting complex release from checkpoint inhibition 1. Beyond hormone receptor regulation, CUEDC2 inhibits nuclear factor-κB activation by interacting with IKK kinases 1, negates heat shock protein 70 chaperone activity 2, and suppresses NLRP3 inflammasome activation in kidney disease 3. In cancer, CUEDC2 promotes Wnt/β-catenin signaling by facilitating β-catenin nuclear translocation, driving triple-negative breast cancer tumorigenesis 4. Clinically, elevated CUEDC2 expression correlates with poor outcomes in breast cancer and extrahepatic cholangiocarcinoma 56. Notably, CUEDC2 has been associated with autism spectrum disorder risk in genome-wide association studies 7. Its expression is disparate across multiple tumor types, implicating CUEDC2 as both a prognostic biomarker and potential therapeutic target in cancer and inflammatory diseases.