Tbpl1, short for TATA box-binding protein-like protein 1, is a crucial transcription-related factor. Unlike TBP, it binds to TATA-less promoters, especially the TCT core promoter element present in many ribosomal protein genes in Drosophila and humans, and is required for their transcription. It also shows a stronger association with TFIIA than TBP. TBPL1 is involved in important biological processes such as cell cycle arrest and apoptosis, and may play a role in regulating some developmental processes like germ cell maturation and differentiation [3,5].

In idiopathic pulmonary fibrosis (IPF), studies using mouse models have provided insights. C-MYC, when up-regulated in IPF mouse lung tissues, activates miR-9-5p which negatively regulates TBPL1 expression. This up-regulation of C-MYC promotes pulmonary fibroblast proliferation and differentiation by inhibiting TBPL1, thus triggering IPF. Conversely, silencing C-MYC retards IPF in mice. Additionally, the C-MYC inhibitor 10,058-F4 inhibits miR-9-5p expression, up-regulating TBPL1 and repressing pulmonary fibrosis [1]. Fluvoxamine, a drug used for depression and anxiety, alleviates bleomycin-induced lung fibrosis in mice by restraining the activation of downstream targets including the PERK/eIF2α/c-Myc/miR-9-5p/TBPL1 signaling pathway [2]. The circadian clock protein REVERBα has been shown to regulate TBPL1; knockdown of REVERBα led to changes in TBPL1, and both affected integrinβ1 focal-adhesion formation and myofibroblast activation in the context of pulmonary fibrosis [4].

In summary, TBPL1 is essential in transcription-related processes and plays a significant role in the development of idiopathic pulmonary fibrosis. Mouse models have been instrumental in revealing its role in this disease area, highlighting its potential as a therapeutic target for IPF treatment.