OPRK1 (opioid receptor kappa 1) is a G-protein coupled receptor that binds endogenous ligands dynorphin and alpha-neoendorphins, as well as synthetic opioids and salvinorin A. Ligand binding triggers G-protein signaling that inhibits adenylate cyclase activity, reduces calcium currents, and increases potassium conductance, ultimately modulating neurotransmitter release 1. The receptor plays established roles in pain perception, physical activity regulation following opioid treatment, and salivary secretion control. Beyond classical opioid signaling, OPRK1 has emerged as a critical regulator in multiple pathological contexts. In prostate cancer, OPRK1 is repressed by androgen receptor (AR) signaling; when AR is inhibited therapeutically, OPRK1 upregulation drives neuroendocrine differentiation through the SLC9A3R1/autophagy/REST axis, promoting treatment-induced neuroendocrine prostate cancer 2. OPRK1 overexpression correlates with worse prostate cancer outcomes and serves as a prognostic biomarker 3. Genetic variations in OPRK1 associate with substance use disorders, with specific polymorphisms (rs6473797, rs963549, rs997917) linked to alcohol and opioid dependence risk 456. In psychiatric disease, differential methylation of OPRK1 in borderline personality disorder correlates with childhood trauma exposure 7. OPRK1 has also been identified as a potential inflammatory biomarker in preeclampsia 8, suggesting broader roles in pregnancy-related pathology.