DDIAS (DNA damage-induced apoptosis suppressor) is an anti-apoptotic protein that suppresses cell death in response to DNA damage and other apoptotic stimuli. Mechanistically, DDIAS inhibits apoptosis through multiple pathways: it blocks death-inducing signaling complex (DISC) formation by interacting with FADD and preventing caspase-8 recruitment 1, and stabilizes caspase-8 by inhibiting its ubiquitin-mediated degradation 1. DDIAS transcription is regulated by NFATc1, a major transcription factor binding to NFAT consensus sequences in the DDIAS promoter 2. DDIAS is significantly overexpressed across multiple cancer types, including colorectal, lung, breast, and hepatocellular carcinoma 3. It promotes tumorigenesis, metastasis, and drug resistance; notably, DDIAS expression confers cisplatin resistance in lung cancer by suppressing apoptosis 2. The NAT10-mediated ac4C modification regulates DDIAS mRNA stability, which promotes HCC progression through the PI3K/AKT signaling axis 4. Additionally, DDIAS was identified as a novel COVID-19 hospitalization risk locus in Latin American populations 5. Clinically, DDIAS represents a promising therapeutic target. Small molecule inhibitors like DGG-100629 suppress lung cancer growth by blocking the NFATc1/DDIAS/STAT3 pathway and overcome gefitinib resistance 6. Targeting DDIAS or its upstream regulators enhances chemotherapy efficacy and represents a novel strategy for treating chemotherapy-resistant cancers.