Age-related macular degeneration (AMD) is the leading cause of vision loss for people aged 50 years and older. Variants in the complement factor H (CFH) gene are associated with an increased risk of developing AMD, making it one of the main drivers for disease progression. Rare mutations that affect the expression of CFH protein and its isoform - Factor H-like protein 1 (FHL-1), have been linked to early-onset macular drusen (EOMD), an inherited degenerative disease with similar clinical characteristics to AMD. Our lab recently found a novel CFH variant of two family members with EOMD. This single nucleotide polymorphism (SNP) in the conserved splice site of intron 3 resulted in a frameshift with premature stop codon and no translation, causing ~50%reduction in CFH/FHL-1 production. Since CFH/FHL-1 are cofactors for C3b cleavage in the alternative pathway of the complement system, this haploinsufficiency will likely affect complement regulation in retinal pigmented epithelial (RPE) cells, hence contributing to the development of AMD-like pathology. Using patient specific iPSC-derived RPE cells, this study aims to investigate the role of CFH/FHL-1 in maintaining complement homeostasis. I will examine the expression levels of several active complement components and multiple regulators of complement activation (RCA). ELISA and Western blots will be used to quantify protein expression, and protein localization was revealed through immunostaining. RPE cells will also be exposed to normal human serum and stained for the membrane attack complex (MAC) to assess the susceptibility of cells to complement-mediated damage. I will also examine reversal of phenotype in EOMD RPE supplemented with exogenous CFH or FHL-1, as well as in Crispr-corrected EOMD iPSC-RPE cells. Results from this study will provide insights into the role CFH/FHL-1 plays in regulating players of the complement pathway RPE cells and its contribution towards progression of AMD.