HSFY1 (heat shock transcription factor Y-linked 1) is a Y chrY-encoded transcription factor with DNA-binding activity specific to RNA polymerase II regulatory regions 1. As a heat shock transcription factor, HSFY1 participates in stress-responsive gene regulation through sequence-specific DNA binding in the nucleus and nucleoplasm 2. HSFY1 is primarily expressed in testicular tissue and plays a role in spermatogenesis, with expression levels showing dosage-independent variation among healthy men but higher overall expression compared to its X chromosome Y 3. In the context of male infertility, HSFY1 transcript isoforms (HSFY1-1 and HSFY1-3) are significantly downregulated in non-obstructive azoospermia patients and serve as potential molecular markers to predict sperm presence in men with meiotic maturation arrest 1. However, HSFY1 deletion studies demonstrate that HSFY genes make only a slight contribution to male fertility, formally excluding them as critical factors required for meiotic progression 4. HSFY1 expression also increases during neural differentiation of embryonic stem cells, suggesting potential roles beyond spermatogenesis 5. Genomic imbalances involving HSFY1 have been identified in Sertoli cell-only syndrome cases, implicating it in spermatogenesis-related pathology 6.