The complement system is a crucial component of the innate immune response, playing a vital role in defending the body against pathogens and maintaining homeostasis. This complex network of proteins acts as a first line of defense, enhancing the ability of antibodies and phagocytic cells to clear microbes and damaged cells. It also participates in inflammation processes and leukocyte recruitment. However, findings regarding a common mutation in the complement component C5 in mouse strains have raised concerns about the validity of numerous studies in immunology, including infectious diseases, inflammatory, autoimmune disorders, and cancer research.