While no CFHR-4 transcription is found in the eye, CFHR-4 accumulates in the choriocapillaris, BrM and drusen, and can compete with FH/FHL-1 for C3b binding, preventing FI-mediated C3b cleavage, highlighting the role of its systemic contribution to AMD pathogenesis. Here, C3 is linked to age-related macular degeneration.