ATIC is a bifunctional enzyme catalyzing the final two steps of purine biosynthesis: formylation of AICAR to FAICAR using 10-formyltetrahydrofolate as a donor, followed by cyclization to IMP 12. Beyond nucleotide metabolism, ATIC promotes insulin receptor autophosphorylation and internalization 3. ATIC deficiency causes AICA-ribosuria, a rare metabolic disorder. Clinically, ATIC is significant in methotrexate (MTX) responsiveness in rheumatoid arthritis: the 347 C/G polymorphism associates with MTX non-response, particularly in European populations 4, with the GG genotype linked to treatment failure (OR=0.741, p=0.009) 4. ATIC acetylation by KAT2B at lysine 266, induced by p53-mediated peroxisomal fatty acid β-oxidation, suppresses ATIC activity and correlates inversely with colorectal cancer progression 5. ATIC expression is significantly upregulated in multiple myeloma with prognostic implications (hazard ratio 1.7) 6, and is epigenetically regulated in hepatocellular carcinoma through p300/CBP-mediated histone acetylation 7. These findings establish ATIC as a metabolic enzyme with diverse roles in disease pathogenesis and therapeutic response.