ADPGK (ADP-dependent glucokinase) is an endoplasmic reticulum-localized enzyme that catalyzes the phosphorylation of D-glucose to D-glucose 6-phosphate using ADP as the phosphate donor 1. Unlike canonical hexokinases that use ATP, ADPGK represents a noncanonical glucose-activating mechanism 1. ADPGK functions as part of an ER-localized glucose sensing system that regulates cellular energy metabolism through modulation of N- and O-glycosylation 2. Loss of ADPGK function impairs the Warburg effect phenotype critical for cell proliferation and causes metabolic catastrophe with increased cell death and ER stress 2. In cancer, ADPGK is upregulated and drives malignant progression: in prostate cancer, ADPGK binds aldolase C (ALDOC) to promote glycolysis via AMPK phosphorylation, with high expression predicting worse overall survival and biochemical recurrence 3. ADPGK is similarly upregulated in breast cancer and included in glycolysis-related prognostic gene signatures predicting survival and immunotherapy response 4. In the tumor microenvironment, ADPGK-AS1 lncRNA influences macrophage metabolic switching toward tumor-promoting M2 phenotypes 5. Additionally, elevated ADPGK expression serves as a biomarker predicting immune-related adverse events in checkpoint immunotherapy across multiple cancer types 67.