GINS4 (GINS complex subunit 4) is a core component of the GINS complex, which is essential for initiating DNA replication and enabling progression of DNA replication forks 1. GINS4 functions as a critical subunit of the CMG (CDC45-MCM-GINS) helicase, the molecular machine that unwinds template DNA during replication and around which the replisome is assembled 2. Beyond canonical replication roles, GINS4 exhibits moonlighting functions in cancer biology. In hepatocellular carcinoma, GINS4 binds to POLE2 and promotes cell proliferation and cycle progression while suppressing ferroptosis via the PI3K/AKT pathway 3. Similarly, in gastric and lung cancers, elevated GINS4 expression correlates with poor prognosis and promotes tumorigenesis through activation of Rac1/CDC42 signaling and stabilization of oncogenic transcripts via interaction with LSH 45. In breast cancer, GINS4 is regulated by a circRNA-miRNA axis and promotes progression 6. Clinically, biallelic GINS4 loss-of-function mutations cause natural killer cell deficiency with neutropenia, with disease severity modulated by allelic expression bias in lineage-committed cells, highlighting GINS4's particular importance in hematopoietic development 78. Notably, GINS4 depletion can induce ferroptosis in cancer cells by destabilizing p53 through Snail-mediated acetylation antagonism 9.