Complement Factor H (CFH) is a key negative regulator of the alternative complement pathway that controls activation of complement component C3 1. CFH functions through multiple mechanisms: it binds heparin and C-reactive protein 2, regulates intracellular C3 levels in macrophages in a cell-autonomous manner 1, and attenuates TNF-α-induced inflammation by upregulating EIF3C 3. CFH is primarily expressed in monocytes and macrophages, where expression increases during inflammation 1. CFH variants are strongly associated with age-related macular degeneration (AMD), with the Y402H polymorphism representing a tyrosine-histidine change in the heparin-binding region that increases AMD risk 7.4-fold in homozygotes 2. CFH deficiency or mutations also predispose to atypical hemolytic uremic syndrome (aHUS), with >70% of aHUS cases harboring CFH mutations or disease-associated polymorphisms 4. CFH mutations in aHUS are associated with early disease onset and high mortality, though patients show variable response to plasma therapy depending on specific mutations 4. Additionally, CFH loss-of-function variants through CFHR5 modulation reduce AMD risk and correlate with enhanced complement activation capacity 5. These findings establish CFH as a critical regulator of complement-mediated inflammation relevant to multiple chr1 diseases.