PROKR2 (prokineticin receptor 2) is a G-protein coupled receptor exclusively coupled to the Gq subclass, mediating calcium mobilization, phosphoinositide turnover, and MAPK activation upon ligand binding 1. Beyond its classical endocrine functions, PROKR2 plays critical roles in sensory processing and neuro-immune regulation. PROKR2-expressing spinal interneurons are essential for pleasant touch sensation and reward encoding, with ablation impairing stress responses and prosocial behaviors 2. ProkR2-bearing sensory neurons regulate anti-tumor immunity via dopamine signaling, enhancing NK cell cytotoxicity in triple-negative breast cancer when stimulated 3. PROKR2 is primarily recognized for its role in reproductive biology. PROKR2 mutations account for autosomal forms of Kallmann syndrome (hypogonadotropic hypogonadism with anosmia) through impaired GnRH neuron migration during development 45. However, PROKR2 mutations also cause normosmic congenital hypogonadotropic hypogonadism, suggesting post-migratory effects on GnRH function 67. Biallelic mutations typically produce complete disease manifestation, while monoallelic mutations show incomplete penetrance and variable expressivity, often with oligogenic inheritance 5. Additionally, PROKR2 dysfunction associates with metabolic and circadian rhythm disturbances 58. The PROK2-PROKR2 pathway thus represents a pleiotropic system with broad implications for reproduction, sensory integration, and immune regulation.