Cfh, or complement factor H, is a complement inhibitor present as a soluble protein and attached to cell surfaces. It is a key player in complement homeostasis, mainly inhibiting excessive activation of the alternative complement pathway [2].

In early-onset macular drusen (EOMD), a novel CFH variant (c.351-2A>G) led to loss of CFH and FHL-1 expression, increased local complement activity, and MAC deposition in EOMD iPSC-derived RPE cells. Nuclease technology correction restored CFH/FHL-1 expression and mitigated alternative pathway complement activity, suggesting CFH haploinsufficiency in EOMD pathogenesis [1]. In a mouse model of atherosclerosis, CFH deficiency limited plaque necrosis in a C3-dependent manner. Deletion of CFH in monocyte-derived inflammatory macrophages increased uncontrolled cell-autonomous C3 consumption, heightened efferocytotic capacity, and reduced plaque size, indicating CFH's role in controlling intracellular C3 levels of macrophages [3].

In conclusion, Cfh plays a crucial role in regulating the alternative complement pathway. Gene-editing models, such as Nuclease technology in EOMD iPSC-derived RPE cells and CFH-deficient mouse models in atherosclerosis, have revealed its significance in macular-related diseases and atherosclerosis. These models help understand the role of Cfh in disease-related biological processes, providing insights for disease-specific research and potential treatment strategies.