In summary (Fig. 11), our findings indicate a dominant role of FHR1 in the patho-mechanism of AMD: (i) FHR1 contributes to MP accumulation in the retina; (ii) EMR2 receptor activation through FHR1 significantly contributes to para-inflammation; (iii) already stressed cells enter the FHR1 signaling prior to manifestation of initial clinical symptoms; (iv) FHR1 facilitates physical interaction between MP and RPE and instigates intracellular second-messenger signaling with the potential to modify RPE’s functional phenotype. The gene discussed is CFHR1; the disease is age-related macular degeneration.