CFHR3 (complement factor H-related 3) is a plasma glycoprotein involved in complement regulation, functioning as a novel complement regulator that inhibits C3 convertase activity and displays anti-inflammatory effects by blocking C5a generation 1. Unlike factor H, CFHR3 lacks strong complement inhibitory activity but binds to C3b and competes with factor H for C3 binding, suggesting a modulatory role in complement control 2. Functionally, CFHR3 suppresses malignant phenotypes in hepatocellular carcinoma, with downregulation promoting cell proliferation and metastasis through the miR-590-3p/CFHR3/STAT3 signaling pathway 3. Low CFHR3 expression correlates with poor HCC prognosis and advanced clinical stage 3. Genetically, CFHR3 alterations are associated with atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy 4, while deletion of CFHR3 and CFHR1 provides protection against age-related macular degeneration (AMD) and IgA nephropathy through enhanced factor H-mediated regulation 15. CFHR3 emerges as a critical regulator of complement-driven pathology and a protective biomarker in multiple kidney and ocular diseases, with therapeutic potential in HCC treatment.