CFHR1 (complement factor H related 1) is a complement regulatory protein that functions as a dimerized inhibitor of complement activation. CFHR1 competes with the physiological complement inhibitor factor H for binding to tissue-bound complement fragments, particularly C3b 1, and can associate with lipoproteins, potentially influencing lipid metabolism. The protein binds to streptococcal collagen-like proteins via its conserved C-terminal short consensus repeats, regulating complement at the C5 convertase and terminal complement complex levels 2. Genetic variations in CFHR1, including deletions and duplications within the complement factor H gene cluster at chromosome 1, are strongly associated with kidney disease pathogenesis 3. A common deletion of CFHR1 and CFHR3 significantly influences IgA nephropathy risk with genome-wide significance 4, while CFHR1 alterations combined with intact CFHR2, CFHR4, and CFHR5 genes associate with atypical hemolytic uremic syndrome 3. Conversely, CFHR1 absence appears protective against age-related macular degeneration (AMD) 1, though FHR1 accumulation promotes chr1 para-inflammatory pathways in AMD tissues via EMR2-dependent signaling 5. Clinically, CFHR1 emerges as a biomarker across multiple diseases: proteome-wide analysis identified it as causally associated with IgA nephropathy 6, elevated in pulmonary fibrosis 7, and highly diagnostic for recurrent pregnancy loss (AUC=0.950) where it drives pathogenesis through complement/coagulation dysregulation 8.