PDYN (prodynorphin) encodes a precursor protein that is processed to generate dynorphin opioid peptides, which function as endogenous ligands for kappa opioid receptors (KORs) 1. The gene belongs to the opioid/orphanin gene family and produces neuropeptides with typical opioid activity 2. PDYN expression is regulated by activity-dependent transcriptional mechanisms, with neuronal stimulation promoting its transcription through conserved enhancer elements that undergo chr20 remodeling 3. The gene is also subject to transcriptional repression by REST in human neuroblastoma cells and adult brain tissue 4. Functionally, dynorphin peptides from PDYN-expressing neurons modulate social behaviors and emotional states. Specifically, dynorphin release from dorsal raphe PDYN neurons activates KORs in the nucleus accumbens, inhibiting serotonin release during social interactions and contributing to social deficits during opioid withdrawal 5. PDYN genetic variants are associated with alcohol use disorder risk and negative emotional drinking behaviors 1, methamphetamine use disorder 6, and depression severity 7. The gene shows altered expression in various neuropsychiatric conditions, suggesting its critical role in mood regulation and addiction vulnerability through modulation of the dynorphin-KOR system.