Cd55, also known as decay accelerating factor, is a membrane lipid microdomain-associated, GPI-anchored protein. It plays a crucial role in shielding cells from complement-mediated attack by accelerating the decay of C3 and C5, regulating the alternative and classical pathways of complement activation [1,4]. It is expressed on all serum-exposed cells and is involved in maintaining normal physiological functions related to complement regulation. Genetic models, such as gene knockout (KO) mouse models, can be used to study its functions in vivo.

In humans, homozygous loss-of-function mutations in the Cd55 gene lead to CD55 deficiency, resulting in hyperactivation of the complement system. This is associated with early-onset protein-losing enteropathy, angiopathic thrombosis, and other symptoms, as seen in the CHAPLE syndrome [2]. In cancer, Cd55 can signal intracellularly through pathways like JNK, JAK/STAT, MAPK/NF-κB, and LCK, promoting malignant transformation, cancer progression, cell survival, angiogenesis, and inhibiting apoptosis. It is also enriched in the cancer stem cell niche of multiple tumors, implicating it in tumor recurrence and chemoresistance [1]. In malaria, erythrocyte Cd55 is specifically required for the internalization of Plasmodium falciparum parasites, suggesting it or its interacting partners may be potential therapeutic targets [3].

In conclusion, Cd55 is essential for regulating the complement system, and its deficiency can lead to various diseases. Studies using genetic models, especially those mimicking loss-of-function mutations, have revealed its roles in diseases such as CHAPLE syndrome, cancer, and malaria. Understanding Cd55's functions provides insights into disease mechanisms and potential therapeutic strategies for these conditions.