LEUTX (leucine twenty homeobox) is a paired-like homeobox transcription factor expressed exclusively during human preimplantation development, specifically at the 4-8 cell stage during zygotic genome activation (ZGA) 1. The gene encodes a DNA-binding transcription factor containing a complete homeodomain and a Leutx-specific domain with transactivation motifs (9aaTAD) 2. Mechanistically, LEUTX functions as a transcriptional activator that targets TAATCC-containing promoters and genomic cis-regulatory sequences overlapping repetitive elements 23. LEUTX stabilizes interactions with histone acetyltransferases EP300 and CBP, opening chr19 and establishing histone acetylation at EGA-related genomic regions 43. This activation upregulates genes critical for preimplantation development and 8-cell markers including DPPA3 and ZNF280A 3. In embryogenesis, LEUTX acts as a primary activator at the 4-cell stage, later balanced by the repressor DPRX at the 8-cell stage 1. Functionally, LEUTX overexpression restores failed embryonic genome activation and improves preimplantation development in cloned embryos 4. Beyond development, LEUTX has been identified as a fusion partner in renal sarcomas with the CIC gene 5. The gene shows rapid evolutionary sequence divergence among primates, with positive selection acting on homeodomain residues 6.