RFC3 encodes a critical subunit of the replication factor C (RFC) complex, which functions as an ATP-dependent DNA clamp loader essential for processive DNA replication by DNA polymerases delta and epsilon 1. The RFC complex loads proliferating cell nuclear antigen (PCNA) onto primed DNA, where PCNA acts as a sliding clamp to enhance polymerase processivity 2. RFC3 contains conserved ATP-binding motifs and exhibits single-stranded DNA-stimulated ATPase activity 1. The protein is essential for cell viability, as RFC3 deletion causes DNA replication defects 2. Beyond its core replication function, RFC3 appears to have regulatory roles in cancer progression. RFC3 is significantly upregulated in multiple cancer types including diffuse large B-cell lymphoma, head and neck squamous cell carcinoma, gastric cancer, and breast cancer, where high expression correlates with poor prognosis and adverse clinical features 345. In gastric cancer, RFC3 is transcriptionally activated by the YAP1/TEAD signaling pathway 5. RFC3 frameshift mutations occur in 24-26% of microsatellite-unstable gastric and colorectal cancers, often resulting in loss of protein expression 6. Additionally, RFC3 contributes to tamoxifen resistance in ER-positive breast cancer through cell cycle regulation 7.