Epigenetically regulated clonally variant expression of the surface variant antigenic proteins like P. falciparum erythrocyte membrane protein 1 (PfEMP1), repetitive interspersed families of polypeptides (RIFINs), and subtelomeric variant open reading frame (STEVOR) over the surface of infected erythrocytes is one of the key strategies adopted by the pathogen for immune evasion. These antigens were encoded by multigene families and high genetic variability in a single infected individual helps the parasite to adapt to a diverse range of host environments and helps in escaping host immune recognition. Among the antigenic variant proteins, RIFINs are the least studied but are known to have a fundamental role in the development of severe malaria by contributing to the rosette formation and immune evasion of the parasite. Conditional deletion of PfCDP (P falciparum Chromo domain protein) protein, which binds to the H3K9me3 modification in P falciparum leads to the selective upregulation of a subset of RIFINs, and the erythrocyte infected with the knockout parasite showed increased rosetting. Since all malaria cases have not developed into severe malaria, we are aiming for the discovery of the potential RIFIN candidate among these six upregulated RIFINs in causing severe malaria by dissecting its role in complement activation, rosetting of RBCs, and inflammation.