Ifi27, also known as IFN-α-inducible protein 27 or ISG12a, is an interferon-stimulated gene. It plays significant roles in immune responses, mitochondrial metabolism, and adipocyte function. It is involved in pathways such as the innate immune response, regulation of the viral life cycle, JAK-STAT signaling pathway, and is crucial for mitochondrial cristae morphogenesis, succinate and fatty acid oxidation [1,2,5].

In adipocytes, Ifi27-knockout leads to reduced expression of key enzymes in the tricarboxylic acid cycle, electron transport chain subunits, and uncoupling protein 1, impairing oxygen consumption and thermogenesis [1,6]. In viral infections, overexpression and knockdown studies in cell lines show that Ifi27 can either positively or negatively regulate viral infections. For example, in dengue, overexpression positively regulated DENV-2 infection, while knockdown had the opposite effect; in HIV-1 infection, Ifi27 upregulation suppressed HIV-1 replication by degrading the Gag protein [2,3]. In COVID-19 patients, elevated Ifi27 expression in the lower respiratory tract is associated with high viral load, and blood Ifi27 expression can predict clinical outcomes [4].

In conclusion, Ifi27 is essential for mitochondrial function and adipocyte thermogenesis. Its role in viral infections and immune responses makes it a potential biomarker and therapeutic target for diseases like dengue, HIV, and COVID-19. The use of gene knockout models has provided valuable insights into its functions in these biological processes and disease conditions [1,2,3,4,6].