RHOXF2 (Rhox homeobox family member 2) is an X-linked transcription factor that plays critical roles in male reproduction and germ cell development. The gene is selectively expressed in human reproductive tissues, with stage-specific expression during spermatogenesis - early germ cells (spermatogonia and early spermatocytes) express RHOXF2/2B, while it is also present in prespermatogonia during fetal testis development 1. RHOXF2 functions by regulating downstream target genes involved in spermatogenesis-related processes including stress protection and cell survival 2. Notably, RHOXF2 exhibits cross-regulatory behavior by targeting RHOXF1, suggesting coordinated transcriptional responses within the RHOX gene cluster 2. The gene has undergone rapid evolution in primates under strong positive selection pressure, with evidence of copy number variation and ongoing selection in human populations 3. Clinically, RHOXF2 mutations have been identified in infertile men with severe oligozoospermia, with functional analysis demonstrating that specific variants (c.202G > A and c.679G > A) significantly impair the protein's ability to regulate downstream genes 2. Additionally, RHOXF2 functions in genome defense by suppressing LINE1 transposition in the male germline, potentially through regulation of the Piwi-interacting RNA pathway 4. Beyond reproduction, RHOXF2 has been implicated in cancer progression, functioning as an oncogene in various malignancies 56.