AK5 (adenylate kinase 5) is a nucleoside monophosphate kinase that catalyzes reversible phosphate transfer between nucleoside triphosphates and monophosphates, with broad nucleoside diphosphate kinase activity. The enzyme regulates ATP metabolism and energy homeostasis, particularly in neural tissues. In cancer biology, AK5 exhibits complex roles depending on tissue context. In gastric cancer, high AK5 expression correlates with poor prognosis and inhibits apoptosis while promoting autophagy and proliferation 1. Similarly, in prostate cancer, AK5 facilitates tumor proliferation, and AK5 inhibitors reduce tumor volume in patient-derived xenografts 2. Conversely, in colorectal cancer, AK5 hypermethylation and subsequent downregulation associate with poor differentiation and metastasis, with AK5 expression regulating AMPK/mTOR signaling 3. In Alzheimer's disease oligodendrocytes, AK5 upregulation activates AMPK signaling, inhibiting neuroinflammation and apoptosis 4. AK5 has emerged as an autoantigen in autoimmune limbic encephalitis, where anti-AK5 antibodies trigger T cell-mediated neuronal damage with poor immunotherapy response 5. Additionally, AK5 was identified as an immunometabolic target in critical COVID-19 severity 6, and rare AK5::ALK gene rearrangements have been identified in pediatric spindle cell neoplasms 7.