SPX (spexin hormone) is a neuropeptide hormone that regulates cardiovascular function and atrial fibrillation susceptibility through interaction with galanin receptors. Spexin acts primarily through galanin receptor 2 (GALR2) to modulate cardiac electrophysiology and protect against atrial fibrillation 1. In patients with atrial fibrillation, plasma spexin levels are significantly reduced compared to healthy subjects, and spexin knockout mice show increased atrial fibrillation vulnerability 1. Mechanistically, spexin binding to GALR2 inhibits CREB phosphorylation, which subsequently downregulates transcription of KCNJ2 (encoding potassium channel Kir2.1) and sarcolipin, leading to reduced inward rectifying K+ current (IK1) and improved calcium handling in atrial myocytes 1. The spexin/GALR2/CREB signaling pathway represents a novel therapeutic target for atrial fibrillation treatment. Beyond cardiac effects, the SPX domain family (named after suppressor of yeast gpa1, phosphatase Pho81, and xenotropic retrovirus receptor XPR1) plays broader roles in cellular homeostasis, particularly phosphate transport regulation 23. However, information about the specific physiological functions of the spexin hormone itself beyond cardiovascular regulation remains limited in the provided literature.