Zishuo Guo, Hongjie Du, Fanyu Yuan, Yuhan Dong, Fangyuan Zhu, Jian Liu, Chengzhilin Li, Xu Guo, Zhaoze Yang, Wenwen Qi, Ming Xia, Chengcheng Liu
ABSTRACT G protein–coupled receptors (GPCRs), the largest family of membrane proteins in mammals, are fundamental to olfactory signal transduction. By detecting odorant molecules and activating G protein–dependent and β‐arrestin–dependent signaling pathways, GPCRs regulate olfactory neuron depolarization, signal transmission, and adaptive modulation. This review comprehensively summarizes the molecular mechanisms of GPCRs in olfactory perception, signaling network regulation, and olfaction‐related disorders, including olfactory dysfunction, neurodegenerative diseases, and allergic inflammation. Furthermore, it highlights emerging therapeutic strategies such as biased ligands targeting GPCRs and stem cell–based interventions with clinical potential. Future investigations should prioritize elucidating the functions of orphan receptors and advancing precision therapeutic technologies to achieve breakthroughs in the diagnosis and treatment of olfaction‐related disorders.