FN3K (fructosamine-3-kinase) is a metabolic kinase that mediates protein deglycation by phosphorylating fructoselysine residues on glycated proteins, converting them to fructoselysine-3-phosphate adducts that decompose under physiological conditions 123. This enzyme prevents accumulation of irreversible advanced glycation end-products (AGEs) 4. FN3K operates in multiple cellular compartments including the cytosol and mitochondria, with documented activity in erythrocytes 3. Mechanistically, FN3K recognizes and binds glycated substrate proteins through specific catalytic-domain residues 56. The enzyme also functions in oxidative stress response by deglycating NRF2 (NFE2L2), a critical transcription factor controlling cellular stress programs 7. Glycation impairs NRF2 function, and FN3K-mediated deglycation restores NRF2 stability and transcriptional activity 7. Clinically, FN3K activity exhibits substantial interindividual variability determined by genetic polymorphisms in the FN3K promoter and exon 6 8. This variability impacts glycation at specific hemoglobin sites but not overall HbA1c levels 8. NRF2-dependent tumorigenesis in hepatocellular carcinoma requires FN3K 7, positioning FN3K as a potential therapeutic target in cancer 9. FN3K activity also correlates with kidney disease status 10.