C4BPB encodes the beta chain of complement component 4-binding protein (C4BP), a plasma glycoprotein that negatively regulates the classical complement pathway 1. As a cofactor for C3b/C4b inactivator, C4BPB-derived protein facilitates C4b hydrolysis and accelerates C4bC2a complex degradation, thereby controlling complement activation 1. The C4BPB gene is transcriptionally regulated by hepatocyte nuclear factor-3 and nuclear factor-I/CTF in hepatocytes, with differential regulation of C4BPA and C4BPB ensuring balanced isoform production during acute phase responses 21. The beta chain specifically binds anticoagulant protein S, linking C4BP to coagulation regulation 3. Genome-wide association studies identified C4BPB/C4BPA variants associated with venous thrombosis risk through protein S-independent mechanisms 4. Beyond hemostasis, C4BP(β-) demonstrates immunomodulatory properties that attenuate inflammation in colitis models and myeloid cells from inflammatory bowel disease patients, suggesting therapeutic potential 5. C4BPB expression is elevated in hepatocellular carcinoma plasma extracellular vesicles, implicating complement cascade involvement in cancer progression 6. Notably, the murine C4BPB gene has become a pseudogene, limiting translational research 3.