TPRX1 (tetrapeptide repeat homeobox 1) is a critical transcription factor that regulates zygotic genome activation (ZGA) during early human embryonic development. TPRX1 belongs to the eutherian totipotent cell homeobox (ETCHbox) family and is highly translated around the time of ZGA 1. As a key executor of ZGA gene networks, TPRX1 binds to regulatory DNA sequences containing the 5'-TAATCC-3' motif and activates expression of essential ZGA marker genes including NANOGNB, ZSCAN4, DUXB, KLF5, and DPPA3 1. Loss-of-function studies demonstrate that TPRX1 knockdown leads to defective ZGA and impaired preimplantation development 1. TPRX1 serves as a marker protein for human 8-cell-like cells (8CLCs), which transcriptionally resemble 8-cell human embryos and express ZGA markers 2. The gene is regulated by maternal transcription factor OTX2, which promotes TPRX1 activation at the four-cell stage 3. Notably, TPRX1 is absent in mice but present in humans, highlighting species-specific regulation of early embryogenesis 4. This transcription factor represents a fundamental component of the molecular machinery controlling the maternal-to-zygotic transition, making it essential for successful human embryonic development and totipotency establishment.