Considering the fertility defect in heterozygous Rspo2 mutant mice, the severe follicular growth defect in Rspo2 homozygous mutant ovaries and the conservation of RSPO2 expression in ovaries in a little girl, we can assume that RSPO2 is a candidate gene for premature ovarian insufficiency (POI) in women. Here, RSPO2 is linked to Premature ovarian insufficiency.