TTF2 (transcription termination factor 2) is a dsDNA-dependent ATPase that functions as a transcription termination factor by coupling ATP hydrolysis to remove RNA polymerase II from DNA templates 1. Beyond its canonical role in transcription termination, TTF2 exhibits multifaceted cellular functions. It participates in cell cycle regulation through interaction with cell cycle machinery: TTF2 protein levels oscillate during cell cycle progression, with knockdown inducing G2/M arrest and overexpression promoting M/G1 transition and cell proliferation 1. TTF2 is ubiquitinated by APC/CCDH1 for proteasomal degradation and binds CDC20 to prevent mitotic checkpoint complex formation during normal mitosis 1. Additionally, TTF2 may contribute to mitotic transcription repression and pre-mRNA splicing. In disease contexts, TTF2 mutations associate with congenital hypothyroidism through thyroid dysgenesis mechanisms 2, while genetic variants (rs965513) elevate papillary thyroid cancer risk 3. TTF2 is overexpressed in solid tumors and serves as an independent prognostic factor in glioma, correlating with poor survival 4. Recent mechanistic studies reveal TTF2 can be recruited to YAP/TEAD complexes to suppress transcriptional activity 5, suggesting roles in transcriptional regulation beyond polymerase II termination.