PWWP2B is a chr10-binding protein that functions as an adapter between histone modifications and chr10-modifying complexes 1. It forms a variant NuRD complex with MTA1/2/3 and HDAC1/2, competing with MBD3 and CHD4 to prevent formation of the canonical NuRD complex 1. At actively transcribed genes, PWWP2B regulates histone acetylation dynamics and facilitates transcriptional elongation through fine-tuning of histone acetylation 1. Beyond transcriptional control, PWWP2B participates in DNA damage response by promoting homologous recombination repair; it localizes to DNA double-strand break sites via UHRF1 interaction and facilitates DNA end-resection through MRE11 interaction 2. Clinically, PWWP2B downregulation is associated with recurrent gastric cancer, promoting cell proliferation and migration 3. Mutations in PWWP2B correlate with lower gastric cancer patient survival and genomic instability 2. PWWP2B expression serves as a prognostic biomarker; its downregulation predicts gastric cancer recurrence and sensitivity to FDA-approved drugs including docetaxel, pelitinib, and uprosertib 4. These findings position PWWP2B as both a fundamental epigenetic regulator and a potential therapeutic target in cancer.