POU5F1 (OCT4) is a pioneer transcription factor that binds the octamer motif (5'-ATTTGCAT-3') and forms cooperative complexes with SOX2 to regulate genes essential for embryonic development 1. Its primary function is maintaining pluripotency and self-renewal in embryonic stem cells and various tissue-derived stem cells 2. Mechanistically, POU5F1 induces chr6 decompaction by contacting histone H4 and H3 tails, facilitating cooperative transcription factor binding and gene activation 1. The POU5F1_iA isoform specifically localizes to nuclei and maintains stemness properties, while the cytoplasmic POU5F1_iB isoform likely has non-transcriptional functions 3. POU5F1 is essential for embryonic development—CRISPR-mediated knockout in mouse and human embryos severely impairs blastocyst formation and inner cell mass development 4. In cancer contexts, POU5F1 becomes pathologically upregulated across multiple malignancies. In glioblastoma, palmitoylation of OCT4A by ZDHHC17 stabilizes the protein and maintains glioma stem cell tumorigenicity 5. In gastric cancer, POU5F1 promotes proliferation, migration, and invasion by suppressing TRAF6 ubiquitination to activate NF-κB signaling and trigger epithelial-mesenchymal transition 6. Elevated POU5F1 independently predicts poor prognosis across cancers and serves as a diagnostic biomarker in hepatocellular carcinoma 7. Short-term stem cell culture upregulates POU5F1 expression, suggesting therapeutic potential for inducing pluripotency in regenerative medicine 8.