Tcof1, also known as Treacle Ribosome Biogenesis Factor 1, encodes a nucleolar protein that regulates ribosomal DNA (rDNA) transcription. It is involved in multiple cellular processes such as cell cycle progression, stress sensing, and DNA damage response [2,3]. Mutations in Tcof1 are associated with Treacher Collins syndrome (TCS), a rare genetic disorder characterized by severe craniofacial deformations [1,3].

In TCS, over 200 pathogenic variants in Tcof1 have been identified, most of which are deletions leading to a frame-shift and formation of a termination codon [1]. Bioinformatic analysis of Tcof1-related molecular networks in TCS showed that Tcof1-related genes are enriched in various biological processes like cell proliferation, apoptosis, cell cycle, differentiation, and migration, and in signaling pathways such as the ribosome, p53, cell cycle, and WNT signaling pathways [6]. Tcof1 haploinsufficiency promotes early T cell precursor-like leukemia in NrasQ61R/+ mice [7]. In addition, Tcof1 has been implicated in cancer development. In colorectal cancer, Tcof1 promotes progression by stabilizing β-catenin [2]. In hepatocellular carcinoma (HCC), Tcof1 expression is elevated, coordinating oncogenic activation and rRNA production to promote tumorigenesis, and it also has an impact on antitumor immune responses [4]. In triple-negative breast cancer (TNBC), Tcof1 upregulation promotes stemness and tumour growth and correlates with poor prognosis [5].

In conclusion, Tcof1 is a crucial regulator of cellular processes. Its study through genetic models like Tcof1 haploinsufficient mice has revealed its role in TCS, cancer development, and other disease conditions. Understanding Tcof1 helps to decipher the molecular mechanisms underlying these diseases, potentially providing new therapeutic targets.