DIDO1 (death inducer-obliterator 1) is a multifunctional protein that regulates cell differentiation, apoptosis, and transcriptional processes. In embryonic stem cells, DIDO1 is a target of master pluripotency factors Oct4, Sox2, and Nanog, and functions to maintain self-renewal through feedback regulation of these factors 1. DIDO1 contains a SPOC domain that acts as a phosphoserine-binding module, enabling interaction with the RNA polymerase II C-terminal domain and bridging transcription machinery with co-transcriptional regulators including splicing and RNA modification factors 2. DIDO3, the largest isoform encoded by DIDO1, is essential for accurate mRNA splicing and transcription termination; its deletion causes hepatitis, testicular degeneration, and progressive ataxia in mice 3. Disease relevance: DIDO1 dysregulation contributes to multiple pathologies. Circular RNA-derived DIDO1 (circDIDO1) functions as a tumor suppressor in gastric cancer, inhibiting cell proliferation and metastasis through PARP1 and PRDX2 interaction 4. In melanoma, BMP-induced DIDO1 upregulation promotes tumor progression via Integrin αV signaling 5. DIDO1 expression correlates with esophageal squamous cell carcinoma progression depth 6. Serum anti-DIDO1 antibodies serve as predictive biomarkers for acute ischemic stroke risk 7. Additionally, dengue and Zika viruses exploit DIDO1 as a host factor necessary for viral replication through interaction with viral NS1 protein 8.