ADCY3 encodes adenylate cyclase 3, a ciliary enzyme that catalyzes cAMP synthesis in response to G-protein coupled receptor signaling 1. In olfactory epithelium, ADCY3 is activated by the G-protein GNAL to mediate odorant receptor signaling [UniProt]. Beyond chemosensation, ADCY3 functions as a critical metabolic regulator in hypothalamic neurons, where its ciliary localization influences food intake and body weight regulation 23. ADCY3 dysfunction contributes to obesity through multiple mechanisms: genetic variants associated with increased body weight have been identified in human populations 1, while epigenetic silencing via DNA methylation promotes fat accumulation 4. In brown adipose tissue, ADCY3 generates a cold-inducible truncated isoform that negatively regulates thermogenic cAMP production, acting as a "rheostat" to prevent excessive energy dissipation 5. Sex-specific effects occur with ADCY3 dysfunction: males show increased food intake-driven adiposity and behavioral changes, while females exhibit reduced energy expenditure and anxiety-like behavior 6. Notably, ADCY3 signaling operates independently from leptin pathways in regulating fat accumulation 7. ADCY3 represents a promising anti-obesity drug target, with emerging evidence suggesting therapeutic potential through pharmacological activation or modulation of its ciliary localization 1.