In both CFH(Y/Y) and CFH(H/H)-iRPE, the AMD disease phenotypes are mediated by C3a–C3aR1 and C5a–C5aR1 signaling-induced NF-κB activation, autophagy downregulation, and dysregulated intracellular calcium homeostasis. The gene discussed is NFKB1; the disease is age-related macular degeneration.