RTRAF (RNA transcription, translation and transport factor), also known as C14orf166, is a 28 kDa nuclear and cytoplasmic protein that functions as a core component of the human tRNA ligase complex 1. Its primary role involves RNA metabolism, including tRNA splicing and RNA transport 1. RTRAF associates with DDX1, HSPC117, and FAM98B to form a transcription-dependent RNA transport complex that shuttles between nucleus and cytoplasm, suggesting a prominent role in regulating nuclear and cytoplasmic RNA fate 2. The protein interacts with RNA polymerase II and positively modulates its transcriptional activity 3. In viral infection, RTRAF binds to influenza A virus polymerase PA subunit through its carboxy-terminal region, facilitating viral replication 3. Clinically, RTRAF is significantly upregulated in multiple cancer types including esophageal squamous cell carcinoma, non-small-cell lung cancer, and breast cancer 456. High RTRAF expression correlates with advanced tumor stage, lymph node metastasis, and poor prognosis, functioning as an independent prognostic indicator 45. RTRAF promotes cancer cell proliferation by regulating G1/S transition through suppression of cell cycle inhibitors P21 and P27 6. Additionally, RTRAF dysregulation has been implicated in endocrine disruptor-induced male infertility 7.