PRLHR (prolactin releasing hormone receptor) encodes a G protein-coupled receptor that binds prolactin-releasing peptide (PrRP) and plays a critical role in energy homeostasis and metabolic regulation 1. The receptor primarily functions in the regulation of food intake and energy expenditure, with loss-of-function variants causing excessive weight gain in mice due to decreased energy expenditure rather than increased food intake 2. PRLHR operates through G protein-coupled signaling pathways and is involved in neuropeptide signaling 1. Disease relevance includes associations with cancer risk, where certain PRLHR polymorphisms show protective effects against colorectal cancer in Chinese populations 3. The gene also demonstrates epigenetic alterations in Alzheimer's disease, with increased promoter methylation and decreased expression observed in patient hippocampal tissue, suggesting involvement in neurodegenerative processes 4. Additionally, PRLHR deletions are enriched in neurodevelopmental disorders including ADHD and autism spectrum disorder 5. Recent studies identify PRLHR as essential for Japanese encephalitis virus replication, where its knockdown blocks autophagic flux and inhibits viral infection 6. Clinical significance lies in its potential as a therapeutic target for obesity treatment and as a biomarker for neurodegenerative diseases through liquid biopsy approaches.