TPRX2 is a transcription factor essential for zygotic genome activation (ZGA), the critical transition from maternal to embryonic gene expression control following fertilization 1. As a PRD-like homeobox protein, TPRX2 is highly translated around ZGA and functions as a transcriptional regulator of early embryonic development 2. TPRX2 binds specific DNA sequences containing the 5'-TAATCC-3' motif to activate key ZGA marker genes including NANOGNB, ZSCAN4, DUXB, KLF5, and DPPA3 2. Functionally, TPRX2 knockdown impairs ZGA and preimplantation development, while ectopic expression activates ZGA genes in human embryonic stem cells 2. TPRX2 is upstream-regulated by the maternal transcription factor OTX2, which directly promotes TPRX2 expression to coordinate embryonic genome awakening 3. Despite previous computational predictions suggesting pseudogene status, mass spectrometry studies confirm TPRX2 functions as a bona fide transcriptional activator 4. Notably, TPRX2 exhibits both conserved and divergent regulatory roles across mammalian species; while expressed during bovine preimplantation development, humans lack the TPRX3 ortholog present in cattle, highlighting species-specific regulation of early embryonic transcriptional networks 5.