{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ADP‐dependent glucokinase (ADPGK) is a unique enzyme that phosphorylates glucose to form glucose‐6‐phosphate by using ADP instead of ATP. Structural and biochemical studies have shown that ADPGK exhibits an archaeal‐derived, ribokinase‐like fold with conserved residues critical for its catalytic function, setting it apart from conventional ATP‐dependent hexokinases (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In various human cell types, including tumor cells, ADPGK is abundantly expressed; however, its contribution to canonical glycolysis appears context‐dependent. For instance, while in some tumor lines ADPGK does not evidently alter glycolytic flux under standard conditions, under metabolic stress or when conventional hexokinase activity is compromised, its function becomes critical to maintain cell survival, as observed in studies on certain lung cancer and lymphoma models."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, during T cell receptor stimulation, ADPGK localizes to the endoplasmic reticulum and plays an important role in triggering a metabolic reprogramming toward aerobic glycolysis. This shift, which includes enhanced glucose uptake and redirection of glucose metabolism via mitochondrial shuttles to promote reactive oxygen species generation, is integral to effective T cell activation and signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its metabolic role, ADPGK has attracted attention in the field of cancer immunotherapy. In some studies, loss of ADPGK function precipitates a metabolic catastrophe that compromises tumor survival under high glycolytic demand, while in others its expression renders tumor cells a source of neoantigens for personalized vaccine strategies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}, {"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In addition, recent multi‐omics analyses have identified ADPGK as part of biomarker panels predictive of immune‐related adverse events in cancer immunotherapy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, ADPGK serves as a critical alternative glucokinase that not only adapts cellular glucose phosphorylation under conditions where ATP may be limiting but also modulates metabolic reprogramming in immune cells and tumor contexts. Its multifaceted roles in bioenergetics, stress response, and immunogenicity highlight its potential as both a therapeutic target and a biomarker in metabolic and cancer research.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Susan Richter, Jan P Richter, Sunali Y Mehta, et al. 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