C5 (complement component 5) is a central mediator of the terminal complement pathway that functions through proteolytic cleavage by C5 convertases to generate biologically active fragments C5a and C5b 12. Upon cleavage, C5a acts as a potent anaphylatoxin and chemokine that binds to receptors C5AR1 and C5AR2, triggering G protein-coupled receptor signaling pathways that induce inflammatory responses including intracellular calcium release, smooth muscle contraction, increased vascular permeability, and histamine release from mast cells 1. The C5b fragment initiates formation of the membrane attack complex (MAC), which creates cytolytic pores in target cell membranes 2. C5 activation occurs through all three complement pathways and can be triggered by various stimuli including heme, which induces complement activation via the alternative pathway and promotes thromboinflammation 3. Human skin mast cells can produce C5 protein, though at lower levels than C3, suggesting local complement regulation 4. C5 plays critical roles in bacterial defense, with C5-dependent IL-8 release and phagocytosis being essential for controlling Gram-positive bacterial infections 5. Therapeutic targeting of C5 has shown promise, with inhibitors like eculizumab, gefurulimab, and zilucoplan effectively blocking complement activation and reducing inflammatory responses in various disease contexts 123.