NOBOX (newborn ovary homeobox) is a gonad-specific transcription factor that plays a crucial role in early folliculogenesis and oogenesis 1. The gene encodes a homeobox-containing protein preferentially expressed in primordial and growing oocytes, with expression extending through the metaphase II stage 2. NOBOX binds preferentially to specific DNA sequences and functions as an RNA polymerase II-specific transcription factor regulating oocyte-specific gene expression 1. Biallelic and heterozygous loss-of-function variants in NOBOX are associated with primary ovarian insufficiency (POI), affecting approximately 1-2% of POI cases 3. Recent evidence indicates NOBOX variants account for about 25% of POI cases when considering ethnicity-dependent variant frequencies, though penetrance and expressivity vary significantly 4. Beyond POI, NOBOX variants have been identified in women experiencing oocyte, zygote, and embryo maturation arrest, suggesting roles in post-fertilization development 5. A corrected NOBOX gene model indicates that biallelic variants are most likely pathogenic, with only 14 of previously reported variants remaining causative for POI 6. NOBOX mutations represent a significant genetic contributor to female infertility, making genetic screening clinically relevant for patient management and counseling 7.