Complement C5

Complement C5 is a precursor protein that generates two key immune effectors: the anaphylatoxin C5a and the complement component C5b, both central to the complement cascade (UniProt: P01031). C5b initiates formation of the membrane attack complex (MAC), a multiprotein pore that lysses pathogen cells, while C5a acts as a potent inflammatory mediator and chemokine, binding C5AR1/C5AR2 receptors to trigger calcium signaling, vascular permeability changes, and leukocyte recruitment. These cascades represent foundational mechanisms of innate immunity and pathogen clearance.

C5 operates across the classical, alternative, and lectin complement pathways and is implicated in systemic immune responses. Complement C5 deficiency, a rare genetic condition (MIM 609536), renders patients susceptible to severe recurrent infections, particularly with Neisseria species (UniProt: P01031), demonstrating its critical protective role.

In Alzheimer's disease, C5 is upregulated in human post-mortem AD brain compared to age-matched controls, with a mean log2 fold-change of 0.44 (Chaparral AD proteomics), suggesting complement activation may contribute to neuroinflammatory processes in AD pathology.