TICRR (TOPBP1-interacting checkpoint and replication regulator) is an essential regulator of DNA replication initiation and cell cycle checkpoints in vertebrates 1. The protein functions as the human ortholog of yeast Sld3, facilitating the transition from pre-replication complex (pre-RC) to pre-initiation complex (pre-IC) through stable association with TopBP1 via BRCT motif interactions 1. TICRR plays a critical role in CDK2-mediated loading of CDC45L onto replication origins and participates in selective origin firing by preventing binding of the MTBP-TICRR/TRESLIN complex to dormant origins through interactions with phosphorylated RecQL4 2. During G1, TICRR chr15 binding is independent of loaded MCM complexes but dependent on MTBP association 3. TICRR is essential for normal S/M and G2/M checkpoint function, preventing mitotic entry after ionizing radiation-induced DNA damage; loss of TICRR causes premature mitosis and mitotic catastrophe 1. Clinically, elevated TICRR expression correlates with poor prognosis in multiple cancer types including endometrial cancer, lung adenocarcinoma, and hepatocellular carcinoma, where it promotes proliferation, migration, and epithelial-mesenchymal transition 456. TICRR represents a potential therapeutic target and biomarker for cancer diagnosis and prognosis.