TBP (TATA-box binding protein) is a core general transcription factor that nucleates the TFIID complex, which is essential for initiating RNA polymerase II-dependent transcription 1. As the central component of the TFIID-A module alongside TAF3 and TAF5, TBP recognizes and binds promoter DNA at TATA boxes or TATA-less promoters, facilitating DNA bending and pre-initiation complex (PIC) assembly 12. TBP also participates in RNA polymerase I and III transcription through distinct complexes: the SL1/TIF-IB complex and BRF2-containing complexes, respectively 34. Structurally, cryo-EM studies reveal TFIID adopts multiple conformational states during TBP loading, with initial downstream DNA binding facilitating TATA box scanning 2. Clinically, TBP CAG/CAA repeat expansions (≥46 repeats) cause spinocerebellar ataxia 17 (SCA17/ATX-TBP), characterized by cerebellar ataxia and cognitive dysfunction, with reduced penetrance in the 41-45 repeat range 5. Intermediate TBP expansions (40-42 repeats) can modify the phenotype of STUB1 variants, resulting in marked cognitive impairment 67. Additionally, TATA box polymorphisms affecting TBP binding affinity are associated with hereditary pathologies including thalassemia and cancer predisposition 8.