CFHR5 (complement factor H related 5) is a plasma glycoprotein that functions as a modulator of complement alternative pathway activation 1. The protein binds to C3b complement components and, in dimerized forms, competes with the physiological complement inhibitor factor H for tissue-bound complement fragments 1. However, unlike factor H, CFHR5 lacks strong complement inhibitory activity and instead exhibits complement modulatory properties 1. CFHR5 dysfunction is implicated in multiple diseases. CFHR5 gene alterations, particularly internal duplications of exons 2-3, cause CFHR5 nephropathy, a form of C3 glomerulopathy characterized by abnormal alternative pathway activation and glomerular C3 deposition leading to progressive renal damage and end-stage kidney disease 234. This condition is prevalent in Greek Cypriot populations 4. Conversely, loss-of-function CFHR5 variants reduce age-related macular degeneration (AMD) risk by enhancing complement activation capacity and preserving retinal photoreceptor thickness 5. Elevated plasma CFHR5 levels are associated with venous thromboembolism risk through enhanced thrombin generation and platelet activation 6. Current CFHR5 nephropathy treatments include corticosteroids, immunosuppressive agents, and complement pathway inhibitors, though no disease-specific therapy is established 2.