ZBTB20 is a transcriptional repressor containing zinc finger and BTB domains that functions as a sequence-specific DNA-binding protein 1. Primary functions include regulation of immune responses, where ZBTB20 is a marker gene of regulatory B cells across multiple organs 2, and control of dendritic and synaptic structure critical for neuronal connectivity 3. In cartilage homeostasis, ZBTB20 accumulation in chondrocytes promotes osteoarthritis progression via NF-κB signaling and suppression of PTEN 4. ZBTB20 plays dual roles in cancer: it represses alpha-fetoprotein in adult liver 5, yet its upregulation promotes proliferation and apoptosis resistance in hepatocellular carcinoma, lung cancer, gastric cancer, and glioblastoma 1. T-cell exhaustion markers include ZBTB20 upregulation in colon cancer liver metastases 6. Neurodevelopmental disorder-linked ZBTB20 variants alter dendritic morphology; N-terminal variants affect spine structure while C-terminal variants affect arborization 3. In Alzheimer's disease, ZBTB20-AS1 lncRNA suppresses ZBTB20 expression, promoting GSK-3β/Tau phosphorylation and neurodegeneration 7. ZBTB20 rs9841504 polymorphism reduces gastric cancer susceptibility 8. Clinical applications include potential therapeutic targeting via LATS1 modulation for osteoarthritis and immunotherapy enhancement.