Int Immunopharmacol. 2026 Mar 30;178:116582. doi: 10.1016/j.intimp.2026.116582. Online ahead of print.
ABSTRACT
Cytidine monophosphate kinase 2 (CMPK2) is a pivotal mitochondrial enzyme that plays a multifaceted role in cellular nucleotide metabolism, immune regulation, and disease pathogenesis. This review comprehensively examines the structural characteristics, enzymatic functions, and regulatory mechanisms of CMPK2, emphasizing its significance in maintaining mitochondrial DNA (mtDNA) integrity and energy metabolism. We explore how CMPK2 links mitochondrial stress to inflammation through its involvement in key immune signaling pathways, including the NLRP3 inflammasome and cGAS-STING pathway, thereby modulating innate immune responses. Notably, CMPK2 is upregulated during viral infections, such as SARS-CoV-2 and Zika virus, where it restricts virus replication and enhance antiviral defenses. Furthermore, we discuss the implications of CMPK2 dysregulation in various non-communicable diseases, including systemic lupus erythematosus and neuroblastoma, highlighting its potential as a diagnostic biomarker and candidate therapeutic target. By integrating recent advances in our understanding of CMPK2’s roles across infectious and non-infectious diseases, this review establishes CMPK2 as a pivotal node connecting mitochondrial metabolism, immune responses, and disease mechanisms. Our findings underscore the need for further research to elucidate CMPK2’s complex functions and to explore its therapeutic potential in clinical applications, ultimately contributing to improved disease management strategies.
PMID:41915996 | DOI:10.1016/j.intimp.2026.116582