C4B (complement component 4B) is a key component of the classical and lectin complement pathways that functions in immune defense and regulation. C4B differs structurally and functionally from the related C4A protein, with C4B being more efficient in hemolytic assays while C4A preferentially binds immune complexes 1. The two C4 isotypes together form a duplicated system allowing C3 convertase formation on various substrates, which is vital for eliminating invading microorganisms 1. C4B exhibits significant genetic diversity through copy number variations and allotypic differences, with some variants like the fast-migrating B7 allotype containing amino acid variations in the anaphylatoxin-like region 2. Deficiencies in C4B, caused by gene mutations or copy number reductions, are associated with autoimmune diseases including systemic lupus erythematosus 2. Pathogenic bacteria like Leptospira can exploit C4B by recruiting C4b-binding protein (C4BP) to evade complement-mediated clearance through C4b degradation 3. C4BP itself functions as a fluid-phase complement inhibitor that prevents uncontrolled classical pathway activation and has emerging complement-independent roles in cell survival and immune modulation 4. Clinical significance includes C4B's role in autoimmune disease susceptibility and its potential as a therapeutic target for complement-related disorders.