Jiaming Qi, Yiqun Yu
The olfactory epithelium (OE) maintains lifelong neurogenesis and shows strong regenerative capacity through the coordinated functions of horizontal basal cells (HBCs) and globose basal cells (GBCs). These progenitors are regulated by key transcriptional factors such as Sox2, p63, Pax6, Ascl1, Neurog1 and NeuroD1, as well as signaling pathways including Wnt/β-catenin, Notch, YAP and inflammation-related regulators, which together control lineage specification and injury-induced plasticity. A set of genes such as Lgr5, Tmem59, Notch1, and Chil4 play critical roles in OE homeostasis and regeneration, depending on a broader and highly dynamic network. Recent progress in single-cell transcriptomics, spatial transcriptomics and organoid models has revealed previously unrecognized cell states, differentiation routes and intercellular communications. This review summarizes the molecular and cellular mechanisms that support OE regeneration and highlights emerging technologies that advance understanding the process of olfactory epithelium regeneration and guiding future approaches for restoring olfactory function.