INSL3 is a peptide hormone of the insulin-relaxin family produced exclusively by fetal and postnatal Leydig cells in the testis 1. It serves as a constitutive marker of Leydig cell number and function, independent of hypothalamic-pituitary-gonadal axis regulation 2. During fetal development, INSL3 synthesis begins at weeks 7-8 post-coitum and acts through the G-protein-coupled receptor RXFP2 expressed on gubernacular mesenchymal cells to promote testicular descent, with particular importance during the first phase of descent by thickening the gubernaculum 1. Beyond reproduction, INSL3 regulates feeding through brain Lgr8 signaling; tumor-derived INSL3 induces cancer-associated anorexia by upregulating anorexigenic NUCB1 and downregulating orexigenic neuropeptides 3. INSL3 also influences musculoskeletal health through RXFP2 signaling 4. Disease relevance includes cryptorchidism, where reduced INSL3 and androgen signaling impair testicular descent 5, and primary ovarian insufficiency, where INSL3 mutations contribute to defective folliculogenesis 6. INSL3 functions as a biomarker for Leydig cell differentiation and may be reduced by maternal exposure to endocrine-disrupting chemicals 1. Clinically, INSL3 levels are increasingly recognized as diagnostic markers for testicular pathology beyond research applications 2.