CHR1 (cholinergic receptor muscarinic 3) is a G protein-coupled acetylcholine receptor that mediates cellular responses primarily through phosphoinositide (PI) turnover and calcium signaling 1. The receptor inhibits adenylate cyclase and modulates potassium channels via G protein activation, functioning at synapses and plasma membranes to regulate signal transduction and smooth muscle contraction. Beyond classical cholinergic functions, CHR1 has emerged as critical in brain tumor biology. In glioblastoma (GBM), basal forebrain cholinergic neurons form long-range synaptic connections onto tumor cells, with acetylcholine stimulation through CHR1 inducing sustained calcium oscillations and transcriptional reprogramming that promotes GBM cell motility and progression 23. Similarly, in diffuse midline glioma, cholinergic neuronal activity drives tumor proliferation via CHR1 signaling 1. CHR1 expression is also dysregulated in Alzheimer's disease, where reduced levels correlate with cognitive decline and sleep disturbance, particularly REM sleep regulation 45. In gastric cancer, aberrant CHR1 signaling downstream of PJA2 E3 ligase promotes tumor progression, creating therapeutic vulnerability to muscarinic antagonists 6. These findings establish CHR1 not merely as a classical neurotransmitter receptor but as a critical neuro-oncological mediator linking neural circuits to tumor fitness.