CCDC3 (coiled-coil domain containing 3) is a conserved protein with both extracellular secretory and intracellular nuclear functions 1. As a secreted protein, CCDC3 is highly expressed in adipose tissues and vascular endothelium, where it negatively regulates TNF-α-induced pro-inflammatory responses by inhibiting NF-κB activation in endothelial cells 2. CCDC3 can function in a paracrine/autocrine manner, entering recipient endothelial cells to suppress VCAM-1 expression and inflammatory signaling 2. The protein undergoes N-glycosylation, forms dimeric complexes, and its expression is regulated by insulin, PPARγ agonists, and inflammatory mediators 3. Intracellularly, CCDC3 acts as a tumor suppressor in breast cancer by binding to both p53 and MDM2, protecting p53 from proteasomal degradation without inhibiting ubiquitination 4. This stabilizes nuclear p53, enhancing its transcriptional activity in a positive feedback loop 4. However, conflicting evidence exists regarding CCDC3's role in cancer progression, with some studies showing that CCDC3 knockdown reduces cervical cancer cell proliferation and invasion 56. CCDC3 also responds to hypoxic conditions and may serve as a marker for tissue hypoxia 7.