RRM2 (ribonucleotide reductase regulatory subunit M2) is the small regulatory subunit of ribonucleotide reductase that catalyzes the conversion of ribonucleotides to deoxyribonucleotides (dNTPs), providing essential precursors for DNA synthesis, repair, and replication 1. The enzyme maintains cellular dNTP pools critical for genomic stability and cell cycle progression 2. RRM2 expression is tightly regulated at multiple levels from transcription to translation and plays essential roles in cell proliferation and DNA damage responses 1. In cancer, RRM2 is frequently overexpressed and promotes malignant behaviors including chemotherapy resistance 3. RRM2 mediates drug resistance through both enzymatic and non-enzymatic mechanisms, including stabilization of ANXA1 and activation of the AKT pathway in renal cell carcinoma 4. The protein also regulates tumor immunity and sensitivity to immune checkpoint inhibitors 4. RRM2 is controlled by complex regulatory networks, including the CXCR4/FOXM1/RRM2 axis in small cell lung cancer where FOXM1 directly binds the RRM2 promoter 5. Given its essential role in DNA synthesis and frequent overexpression in resistant cancers, RRM2 represents a promising therapeutic target for enhancing chemotherapy efficacy and overcoming treatment resistance 36.