CHR15 encodes the M5 muscarinic acetylcholine receptor, a G-protein-coupled receptor that mediates cellular responses through Gq/11 signaling, including phosphoinositide breakdown and modulation of ion channels. The receptor plays critical roles in dopaminergic regulation, being expressed in dopamine-containing neurons of the substantia nigra and ventral tegmental area where it regulates mesolimbic dopamine release 1. CHR15 functions in diverse physiological contexts, including hematopoietic stem cell homing through Chr15-eNOS-nitric oxide signaling in bone marrow vasculature 2, and bladder function where variants may contribute to neurogenic bladder dysfunction 3. The receptor's expression is regulated by brain-derived neurotrophic factor (BDNF), with deficiency leading to altered CHR15 levels that can be modulated by environmental enrichment and antidepressant treatments 4. Additionally, CHR15 expression is controlled by myocardin-related transcription factors and serum response factor in smooth muscle cells 5. Clinically, CHR15 genetic variants are associated with increased cigarette consumption and cannabis dependence risk 1, and linkage analysis suggests potential involvement in schizophrenia susceptibility when combined with CHR15 variants 6, highlighting its therapeutic relevance in addiction and psychiatric disorders.