CFHR2 (complement factor H-related protein 2) is a complement regulatory protein composed of four short consensus repeat domains that functions as an alternative pathway complement inhibitor 1. CFHR2 forms homodimers and heterodimers with FHR-1, with dimer composition dynamically regulated by CFHR2 plasma levels 2. The dimerized protein binds C3b and inhibits C3 convertase activity while allowing concurrent factor H-mediated C3b degradation, suggesting cooperative regulation with factor H 1. Genetically, CFHR2 variants associate with multiple complement-mediated diseases: genetic alterations in the CFHR gene cluster link to atypical hemolytic uremic syndrome and C3 glomerulopathy 3, while low-frequency CFHR2 variants independently associate with age-related macular degeneration 4. Therapeutically, CFHR2 supplementation shows promise in neuromyelitis optica spectrum disorder, where decreased serum CFHR2 correlates with disease severity; recombinant CFHR2 and AAV-mediated overexpression reduce complement-mediated neuroinflammation 5. Inverse associations exist between genetically predicted CFHR2 levels and alcohol-related cirrhosis risk 6. CFHR2 is significantly elevated in serum extracellular vesicles from ankylosing spondylitis patients, suggesting potential diagnostic utility 7.