RXFP2 (relaxin family peptide receptor 2) is a G protein-coupled receptor that primarily binds insulin-like peptide 3 (INSL3) to regulate testicular development and male fertility 12. The receptor activates adenylyl cyclase signaling, leading to increased cAMP production upon INSL3 binding 34. RXFP2 plays a crucial role in testicular descent during embryonic development, with expression beginning at embryonic day 14.5 in mouse gubernacula and increasing after birth in cremaster muscle, epididymis, and testicular Leydig and germ cells 56. Beyond developmental functions, RXFP2 is essential for spermatogenesis, with highest expression observed during spermatid maturation stages 14. Biallelic loss-of-function variants in RXFP2 cause autosomal recessive bilateral cryptorchidism and male infertility due to spermatogenic arrest 12, while the well-characterized T222P mutation severely reduces cell membrane expression 5. RXFP2 has also been identified as a risk locus for primary aldosteronism, particularly in males with bilateral adrenal hyperplasia 78. The receptor's function can be disrupted by environmental pollutants, as mixtures of phthalates and bisphenol A reduce RXFP2 signaling responses 3.