Factor I also known as CFI is a serine proteinase that is essential for regulating the complement cascade. Factor I plays a crucial role in the regulation of the complement system, which is essential for both innate and adaptive immunity. This serine protease modulates the complement cascade by cleaving C3b and C4b, thereby preventing excessive inflammation and tissue damage. Factor I primarily circulates in the plasma as a heavily N-glycosylated heterodimer composed of two disulfide-linked chains, each adorned with three N-linked oligosaccharide chains. These glycosylations are vital for Factor I′s interactions with natural substrates and cofactors during catalysis. Factor I requires protein cofactors such as Factor H, CR1, or MCP for the cleavage of C3b, and C4bp or CR1 for the cleavage of C4b, highlighting the importance of these interactions in maintaining immune homeostasis.