L1TD1 (LINE1 type transposase domain containing 1) is a cytoplasmic RNA-binding protein specifically expressed in pluripotent stem cells and certain cancers, derived from the domesticated LINE-1 retroelement ORF1p 1. The protein serves dual functions in maintaining pluripotency and regulating retrotransposition. In human embryonic stem cells, L1TD1 is essential for self-renewal and maintains pluripotency by regulating OCT4 and NANOG expression through interaction with LIN28 and RNA helicase A 2. L1TD1 participates in RNA splicing, translation, protein trafficking, and degradation, bridging nuclear and cytoplasmic regulation 3. Mechanistically, L1TD1 associates with L1 transcripts and interacts with ancestral L1 ORF1p protein, facilitating LINE-1 retrotransposition as an RNA chaperone 1. The protein localizes to ribonucleoprotein condensates and can dissolve stress granules, enhancing translation of specific mRNAs 4. Clinically, L1TD1 shows context-dependent roles in cancer: it acts as a tumor suppressor in non-small cell lung cancer where DNA hypermethylation silences its expression 5, but serves as a positive prognostic marker in colon cancer where increased expression correlates with longer disease-free survival 6. The gene has evolved under positive selection in mammals, suggesting functional importance in genome defense and pluripotency maintenance 7.