CLSPN (claspin) is an essential adapter protein that plays critical roles in DNA replication checkpoint signaling and maintaining genomic stability. The protein functions as a key mediator in the ATR-dependent DNA damage response pathway, facilitating checkpoint-mediated cell cycle arrest in response to replication stress or DNA damage 1. CLSPN directly binds to replication fork DNA and interacts with multiple replisome components including the MCM2-7 complex, TIMELESS-TIPIN, and DNA polymerase ε, positioning it as a central coordinator of replication machinery 1. Mechanistically, CLSPN serves as an adapter that enables ATR-dependent phosphorylation of checkpoint kinase CHEK1 and facilitates proper DNA replication progression. Dysregulated CLSPN expression has significant clinical relevance across multiple cancer types. Overexpression correlates with poor prognosis in prostate cancer, melanoma, hepatocellular carcinoma, and oral squamous cell carcinoma 2345. In these malignancies, CLSPN promotes tumor progression through various mechanisms including activation of Wnt/β-catenin signaling, enhancement of glycolysis, and modulation of the tumor microenvironment 53. Additionally, CLSPN polymorphisms, particularly rs7520495, are associated with oral cancer progression and poor cellular differentiation 6. The protein's involvement in mitotic regulation makes it a potential therapeutic target, as demonstrated by its role in decitabine sensitivity in myeloid tumors 7.