ZBTB14 is a zinc finger and BTB domain-containing transcription factor that functions as both a transcriptional activator and repressor with diverse roles in development, metabolism, and disease. In neural development, ZBTB14 promotes dorsalization of ectoderm by inhibiting BMP signaling and posteriorizes neural tissue by activating Wnt signaling, coordinating dorsal-ventral and anterior-posterior axis patterning 1. ZBTB14 regulates skeletal muscle inflammatory responses through transcriptional control of IL6 and LIF cytokine expression in an AMPK-dependent manner 2. The protein also functions in muscle fiber differentiation, with binding sites enriched in fast glycolytic muscle regulatory programs 3. Disease relevance is significant: ZBTB14 variants are associated with lacunar stroke susceptibility, identified at the ZBTB14-EPB41L3 locus in genome-wide association studies of 7,338 cases and 254,798 controls 4. In breast cancer, ZBTB14 suppresses radiotherapy resistance by transcriptionally repressing TMEM208, with downregulation of ZBTB14 observed in radiotherapy-resistant tumors 5. ZBTB14 promotes non-alcoholic fatty liver disease-associated fibrosis via β-catenin pathway activation in hepatic stellate cells 6. ZBTB14 was identified as a top predicted transcription factor in systemic lupus erythematosus CD4+ T cell dysfunction 7. These findings establish ZBTB14 as a multifunctional regulator with therapeutic potential in vascular, oncologic, hepatic, and autoimmune diseases.