TCOF1 encodes treacle, a nucleolar protein that serves as a central regulator of ribosome biogenesis and RNA polymerase I activity 1. The protein acts as a scaffold, connecting RNA polymerase I with enzymes responsible for ribosomal processing and modification, thereby regulating ribosomal DNA transcription and pre-ribosomal RNA processing 2. TCOF1 is essential for neural crest development, where following monoubiquitination, it associates with NOLC1 to remodel the translational program favoring neural crest specification 1. Loss-of-function mutations in TCOF1 cause Treacher Collins syndrome, an autosomal dominant craniofacial disorder affecting 1 in 50,000 births, characterized by abnormal development of pharyngeal arches leading to microtia, hearing loss, and midface hypoplasia 34. Haploinsufficiency results in neural crest cell depletion through increased cell death in the neuroepithelium 4. Beyond developmental roles, TCOF1 has oncogenic functions in hepatocellular carcinoma, coordinating KRAS activation and rRNA production while affecting immune cell infiltration 5. The protein also maintains mitochondrial homeostasis through FLVCR1-mediated pathways and has been implicated in cellular senescence prevention 67. Variants in TCOF1 have also been associated with human neural tube defects 8.