MCM4 is a core component of the MCM2-7 complex, which functions as the replicative helicase essential for DNA replication initiation and elongation in eukaryotic cells 1. As part of the CDC45-MCM-GINS (CMG) helicase complex, MCM4 participates in unwinding template DNA during replication and serves as a structural scaffold around which the replisome is assembled 2. The six ATPase active sites within the MCM2-7 ring are formed through interactions between neighboring subunits, with MCM4 contributing differentially to overall helicase activity 3. Beyond its canonical replication role, MCM4 is significantly upregulated across multiple cancer types including hepatocellular carcinoma, lung adenocarcinoma, triple-negative breast cancer, and colorectal cancer 456. In hepatocellular carcinoma, MCM4 promotes sorafenib resistance by activating Nrf2 signaling, thereby enhancing ferroptosis evasion 7. MCM4 knockdown arrests cells at G1 phase through P21 induction and suppresses tumor proliferation in lung adenocarcinoma 8. Its expression correlates with poor prognosis and metastatic potential across cancers 5. MCM4 transcription is regulated by the PU.1 transcription factor and can be modulated by natural compounds like trans-resveratrol 9. These findings suggest MCM4 represents a potential therapeutic target in cancer treatment.