SOHLH2 encodes a basic helix-loop-helix (bHLH) transcription factor that plays critical roles in both reproductive biology and cancer. In normal physiology, SOHLH2 is essential for early gametogenesis, specifically functioning in spermatogonial and oocyte differentiation 1. The protein forms functional heterodimers with SOHLH1 and cooperates with SP1 to auto-regulate Sohlh1 gene transcription through E-boxes in the promoter 1. SOHLH2 expression extends beyond gonads to various human tissues, including granulosa cells, theca cells, Sertoli cells, and Leydig cells 2. In reproductive disorders, pathogenic variants in SOHLH2 contribute to premature ovarian insufficiency (POI), with haploinsufficiency effects leading to earlier menopause 345. In cancer biology, SOHLH2 functions as a tumor suppressor, directly binding to and repressing MMP9 promoter activity to inhibit ovarian cancer cell invasion and metastasis 6. Additionally, SOHLH2 suppresses breast cancer angiogenesis by directly repressing HIF1α transcription 7, while also regulating macrophage polarization through LXRα upregulation in triple-negative breast cancer 8. These diverse functions position SOHLH2 as both a critical reproductive development factor and a multi-faceted tumor suppressor.