ZNF461 (zinc finger protein 461) is a KRAB-domain-containing zinc finger transcription factor located on chromosome 19.1 1. The protein contains a KRAB A+B repression domain and eleven C2H2-type zinc finger motifs characteristic of DNA-binding transcription factors 1. ZNF461, also known as gonadotropin-inducible ovarian transcription factor-1 (GIOT-1), is ubiquitously expressed in normal human tissues 1. Mechanistically, ZNF461 functions as a transcriptional corepressor. It is induced by the orphan nuclear receptor Nur77 in response to luteinizing hormone signaling and represses steroidogenic factor 1 (SF-1) transactivation through recruitment of histone deacetylase 2 (HDAC2) 2. In granulosa cells, ZNF461 induction suppresses CYP19 gene transcription through attenuation of SF-1/LRH-1 transactivation 3. Regarding disease relevance, ZNF461 has been identified as downregulated in non-small cell lung cancer (NSCLC) in female never-smokers and may participate in immune response mechanisms associated with NSCLC progression through co-expression with immune-related genes 4. Additionally, ZNF461 gene structure has been disrupted during evolutionary chr19 rearrangements in the gibbon lineage 5, suggesting potential structural vulnerability.