Complement factor H (CFH) (CFH)

Complement factor H (CFH) is a 155 kDa soluble glycoprotein that serves as the primary negative regulator of the alternative complement pathway in human plasma [1]. It is composed of 20 short consensus repeat (SCR) domains, with the C-terminal domain 20 (SCR20) being essential for the protein's ability to distinguish between self and non-self surfaces by binding to host-specific polyanions like sialic acid and glycosaminoglycans [2, 3]. Mutations in domain 20 are a hallmark of atypical hemolytic uremic syndrome (aHUS), as they impair the protection of host endothelial cells from complement-mediated attack without necessarily affecting fluid-phase regulation [2]. In the context of age-related macular degeneration (AMD), CFH dysfunction leads to chronic inflammation and tissue damage in the retina [4]. Therapeutic interventions include recombinant Factor H (e.g., GEM103) and engineered fusion proteins (e.g., TT30) that aim to restore regulatory control and protect host tissues from overactive complement signaling [4, 5].

Other names

Factor HH factor 1HFHF1HF2Complement factor H domain 20SCR20CFAH

Acts as a cofactor for Factor I-mediated cleavage of C3b into iC3b and accelerates the decay of the alternative pathway C3-convertase (C3bBb) [1, 3].