SMIM20 (small integral membrane protein 20) is a gene encoding a peptide precursor for phoenixin, a pleiotropic neuropeptide with roles extending beyond reproduction. Phoenixin is generated through proteolytic cleavage of SMIM20 and mediates its biological functions primarily via GPR173 receptor activation 1. In the reproductive system, phoenixin potentiates luteinizing hormone secretion, controls estrus cycle timing, and stimulates oocyte maturation 21. The peptide operates through PKA-dependent signaling in hypothalamic neurons and modulates kisspeptin and GnRH gene expression 2. Beyond reproduction, phoenixin exerts anxiolytic and anti-inflammatory effects while supporting memory and energy metabolism 1. In adipose tissue, phoenixin promotes white adipogenesis through cAMP/Epac-dependent pathways, with serum levels positively correlating with BMI 3. SMIM20 is expressed throughout the gastrointestinal tract and regulates food intake 4. At the molecular level, SMIM20 DNA methylation inversely associates with oxidative stress biomarkers and mediates metal-induced oxidative DNA damage 5. Clinically, dysregulation is implicated in endometriosis, where reduced phoenixin levels impair ectopic endometrial function 6. A SMIM20-derived long non-coding RNA shows poor prognostic value in acute myeloid leukemia 7.