TBX1 is a T-box transcription factor encoded on chromosome 22.2 that serves as a master regulator of embryonic development, particularly cardiovascular and craniofacial systems 1. The gene functions through epigenetic modifications rather than as a strong transcriptional activator or repressor, regulating diverse developmental processes 1. TBX1 is haploinsufficient, meaning loss of a single copy can cause disease 1. Mechanistically, TBX1 promotes pharyngeal arch segmentation and cardiac morphogenesis, working upstream of thymus and parathyroid gland development from the third pharyngeal pouch. After myocardial infarction, TBX1 in lymphatic endothelial cells promotes an immunosuppressive microenvironment through chemokine Ccl21 and integrin Icam1, facilitating cardiac repair 2. Clinically, TBX1 loss-of-function mutations cause 22q11.2 deletion syndrome (DiGeorge/velocardiofacial syndrome), the most common microdeletion syndrome affecting ~1:2000 individuals 34. This syndrome presents with conotruncal heart malformations including tetralogy of Fallot and ventricular septal defects 56, palatal defects, thymic hypoplasia causing immunodeficiency, hypocalcemia from parathyroid dysfunction, and neurodevelopmental abnormalities 6. Conversely, 22q11.2 duplication syndrome causes variable phenotypes including congenital heart disease, gastrointestinal complications, and developmental delays 7. The phenotypic severity correlates with the chr22 region affected, with TBX1 loss being the primary driver of cardiac and craniofacial manifestations 3.