ZDBF2 (zinc finger DBF-type containing 2) is a paternally expressed imprinted gene that plays a critical role in genomic imprinting regulation through a unique transient mechanism. The gene exhibits paternal allele-specific expression in various embryonic and adult tissues, except for placenta and adult testis which show biallelic expression 1. ZDBF2 imprinting is regulated by a novel mechanism involving a transient paternal transcript (GPR1-AS in humans, Liz/Zdbf2linc in mice) that arises from the unmethylated paternal allele and establishes secondary epigenetic marks to maintain ZDBF2 expression 2. This imprinting mechanism originated evolutionarily through insertion of a MER21C long terminal repeat retrotransposon in the common ancestor of Euarchontoglires 2. The gene demonstrates dynamic genomic imprinting, with maternal germline differentially methylated regions controlling transient expression patterns that switch from maternal to paternal imprinting during embryonic development 3. ZDBF2 has clinical relevance beyond development, as it has been identified as upregulated in aging skeletal muscle through artificial neural network analysis 4 and associated with treatment-resistant schizophrenia through polygenic overlap with BMI 5. The gene also shows involvement in cancer contexts, with mutations identified in canine gastrointestinal lymphoma 6.