FHIT encodes a dinucleoside triphosphate hydrolase located at the fragile site FRA3B on chromosome 3.2. The protein catalyzes hydrolysis of diadenosine triphosphate (Ap3A) to AMP and ADP 1, and exhibits additional enzymatic activities including adenylylsulfatase and adenylylsulfate-ammonia adenylyltransferase functions 2. Beyond its catalytic role in purine metabolism, FHIT functions as a tumor suppressor through multiple mechanisms: it inhibits MDM2-mediated p53 degradation to promote p53-dependent apoptosis 3, modulates CTNNB1-dependent transcription of proliferation genes 4, and enhances mitochondrial calcium uptake to sensitize apoptosis pathways 5. Loss of FHIT expression is among the most common alterations in human cancers including lung, esophageal, gastric, breast, and cervical malignancies 6. Recent evidence reveals FHIT functions as a genome "caretaker" whose loss causes nucleotide imbalance, replication stress, and spontaneous DNA breaks, generating a mutator phenotype that accelerates genomic instability 7. Reduced FHIT expression correlates with poor prognosis, advanced TNM staging, and lymph node metastasis in breast cancer 8. Epigenetic silencing via promoter methylation represents a common mechanism of FHIT inactivation in liver cancer 9.