C4b-binding protein (C4BP) is a glycoprotein synthesized in the liver, circulating at ~200 µg/mL in plasma, and functioning as a key inhibitor of the classical and lectin complement pathways. Its octopus-like structure comprises seven α-chains (70 kDa each) and one β-chain (40 kDa) in the predominant isoform (α7β1), though β-deficient isoforms (α7β0, α6β1) exist, with α7β0 upregulated during acute inflammation. The α-chain complement control protein (CCP) domains 1–3 mediate binding to C4b and heparin, while the β-chain interacts with protein S, forming a calcium-dependent complex critical for anticoagulant activity. C4BP accelerates decay of C3/C5 convertases and acts as a cofactor for factor I in proteolytic cleavage of C4b/C3b, preventing excessive complement activation.

Clinically, C4BP is implicated in neurodegenerative, autoimmune, and oncological disorders. In Alzheimer’s disease, C4BP binds amyloid-β plaques and apoptotic neurons, mitigating neuroinflammation by limiting complement-mediated damage. Elevated plasma C4BP correlates with psoriasis severity, where it modulates alternative pathway activation in skin lesions.