ZBTB7B (zinc finger and BTB domain containing 7B) is a tissue-specific transcription factor with primary roles in T cell lineage commitment and metabolic regulation. In T cells, ZBTB7B (also known as ThPOK) is necessary and sufficient for CD4+ lineage commitment by suppressing RUNX3 expression and recruiting histone deacetylases to silence the CD8 locus 1. It controls TRIB2 transcription to regulate naive CD4+ T cell homeostasis during aging 1. Beyond immunity, ZBTB7B functions as a metabolic regulator: it is implicated in obesity through rare coding variants affecting energy expenditure 2, regulates hepatic gene expression and suppresses hepatocellular carcinoma initiation by repressing c-Jun 3, and controls SERPINA3 expression in liver fibrosis pathogenesis 4. In the gastric epithelium, ZBTB7B regulates pit cell differentiation 5. ZBTB7B's dysregulation associates with disease: epigenetic hypomethylation correlates with increased inflammatory cytokine production in ulcerative colitis 6, and a CTSLHighZBTB7BLow gastric cancer subtype exhibits immune evasion features 7. Additionally, ZBTB7B is downstream of ALDH1A1 in regulating tumor glycolysis and immune escape 8. These findings establish ZBTB7B as a pleiotropic regulator controlling T cell fate, metabolic homeostasis, and tumor suppression across multiple tissues.