CFHR4 (complement factor H-related 4) is a plasma glycoprotein involved in complement regulation and C3b binding 1. Unlike factor H, CFHR4 lacks strong complement inhibitory activity but exhibits regulatory functions 1. CFHR4 binds native pentameric C-reactive protein in a calcium-dependent manner and facilitates CRP recruitment to necrotic cells, suggesting a role in opsonization 2. Genetically, CFHR4 alterations within the CFHR-Factor H gene cluster are associated with kidney diseases including C3 glomerulopathy and atypical hemolytic uremic syndrome 3. In hepatocellular carcinoma (HCC), CFHR4 expression is significantly downregulated in tumor tissue compared to normal liver 4. Low CFHR4 expression correlates with advanced TNM stage, higher histological grade, elevated AFP levels, and poor prognosis 45. CFHR4 inversely correlates with certain immune cell infiltrates (Th2, NK CD56bright, Tfh cells) and positively correlates with others (dendritic cells, neutrophils, Th17 cells) 5. CFHR4-positive hepatocytes are associated with reduced therapeutic benefit in advanced HCC treated with combination chemotherapy 6. Additionally, CFHR4 appears dysregulated in non-alcoholic fatty liver disease and acute cerebral infarction, suggesting broader metabolic and inflammatory roles 78.