T-box transcription factor TBX3 is a protein that in humans is encoded by the TBX3 gene. T-box 3 (TBX3) is a member of the T-box gene family of transcription factors which all share a highly conserved DNA binding domain known as the T-box. The T-box gene family consists of 17 members in mouse and humans that are grouped into five subfamilies, namely Brachyury (T), T-brain (Tbr1), TBX1, TBX2, and TBX6. Tbx3 is a member of the Tbx2 subfamily which includes Tbx2, Tbx4 and Tbx5. TBX3 has domains which are important for its transcription factor function which include a DNA-binding domain (DBD) also called the T-box, a nuclear localization signal, two repression domains (R2 and R1) and an activation domain (A). TBX3 can activate and/or repress its target genes by binding a T-element, or half T-element sites. The function of TBX3 as either a transcriptional repressor or transcriptional activator is, in part, modulated by protein co-factors. In humans, heterozygous mutations of TBX3 lead to the autosomal dominant developmental disorder, ulnar mammary syndrome (UMS), which is characterized by a number of clinical features including mammary and apocrine gland hypoplasia, upper limb defects, malformations of areola, dental structures, heart and genitalia. Tbx3 is expressed in heterogenous populations of hypothalamic arcuate nucleus neurons which control energy homeostasis by regulating appetite and energy expenditure and the ablation of TBX3 function in these neurons was shown to cause obesity in mouse models. Importantly, Tbx3 was shown to be a key player in driving the functional heterogeneity of hypothalamic neurons and this function was conserved in mice, drosophila and humans.