Abstract
Adenylate kinases (AKs) are important enzymes involved in cellular energy metabolism. Among AKs, AK5 (adenylate kinase 5), a cytosolic protein, is emerging as a significant contributor to various diseases and cellular processes. This comprehensive review integrates findings from various research groups on AK5 since its discovery, shedding light on its multifaceted roles in nucleotide metabolism, energy regulation, and cellular differentiation. We investigate its implications in a spectrum of diseases, including autoimmune encephalitis, epilepsy, neurodegenerative disorders such as Alzheimer's and Parkinson's, diabetes, lower extremity arterial disease, celiac disease, and various cancers. Notably, AK5's expression levels and methylation status have been associated with cancer progression and patient outcomes, indicating its potential as a prognostic indicator. Furthermore, AK5 is implicated in regulating cellular processes in breast cancer, gastric cancer, colorectal carcinoma, prostate cancer, and colon adenocarcinoma, suggesting its relevance across different cancer types. However, a limitation lies in the need for more robust clinical validation and a deeper understanding of AK5's precise mechanisms in disease pathogenesis, despite its association with various pathophysiological conditions. Nonetheless, AK5 holds promise as a therapeutic target, with emerging evidence suggesting its potential in therapy development.