TBPL1 (TATA-box binding protein like 1) is a specialized transcription factor that functions as part of a TATA-less transcription system, distinct from the classical TBP-mediated pathway. TBPL1 primarily mediates transcription of ribosomal protein genes through binding to the 5'-TCT-3' core promoter element, rather than the TATA box 1. The protein localizes to nucleoli and works in conjunction with PAF1 to regulate RNA polymerase II transcription at ribosomal DNA intergenic spacers, maintaining proper nucleolar organization and rRNA biogenesis 2. TBPL1 shows stronger association with TFIIA compared to TBP and can synergize with other transcription factors like geminin in activating TATA-less promoters such as NF1 31. Disease relevance includes roles in cancer biology, where TBPL1 expression is dysregulated in colorectal and breast cancers, with miR-133b acting as a tumor suppressor by negatively regulating TBPL1 45. Additionally, TBPL1 is involved in pulmonary fibrosis through regulation by REVERBα, affecting myofibroblast activation and integrin β1 focal-adhesion formation 6. The protein also participates in cellular senescence pathways and has been implicated in various developmental processes 78.