TGIF2LY is a Y-linked transcription factor that may function as a transcriptional regulator in testis and potentially compete with or regulate TGIF2LX [UniProt]. The gene encodes a DNA-binding protein with transcription repressor activity specific to RNA polymerase II, capable of binding chrY and cis-regulatory regions [GO annotations]. TGIF2LY has clinical relevance to male fertility: heterozygous truncating variants were validated as a likely cause of primary spermatogenic failure in an analysis of 521 infertile men, with LP/P variants identified in multiple subjects with azoospermia, oligozoospermia, or cryptorchidism 1. During early embryonic development, TGIF2LY shows higher expression in undifferentiated human embryonic stem cells compared to differentiated embryoid bodies, suggesting a role in maintaining pluripotency rather than lineage-specific differentiation 2. Additionally, TGIF2LY exhibited differential expression in endometrial microchimerism studies, with elevated expression in infertile patients compared to fertile controls 3. The gene's involvement in transcriptional regulation and its association with male infertility suggest TGIF2LY plays an essential role in spermatogenesis and reproductive development.