Negr1, or neuronal growth regulator 1, is a GPI-anchored cell adhesion molecule in the immunoglobulin LON family. It has been implicated in regulating neurite outgrowth, synapse formation, and is associated with mood regulation, energy balance, and behavior regulation [1,5]. It is involved in pathways such as the Negr1-Fgfr2 pathway related to synaptic plasticity [3]. Genetic models like Negr1-deficient (negr1-/ -) mice are valuable for studying its functions.

In negr1-/-mice, anxiety-and depression-like behaviors increase, along with decreased adult hippocampal neurogenesis, compromised LTP and mEPSC in the dentate gyrus, and reduced lipocalin-2 (Lcn2) expression in the hippocampus. Heterologous Lcn2 expression in the hippocampal DG of these mice can rescue the abnormal behaviors and restore neurogenesis and mEPSC frequency [1]. In addition, Negr1-/-mice show abnormal olfactory habituation and dishabituation, increased inhibitory inputs to mitral cells in the olfactory bulb, decreased excitability, and diminished adult neurogenesis in the subventricular zone, affecting affective discrimination [2]. Also, Negr1-/-male mice have alterations in monoaminergic neurotransmission, enhancing time-dependent sensitization to amphetamine [6]. In the salivary glands of Negr1 KO mice, salivation is decreased, and there are changes in intracellular Ca2 + and ion channel activities [4].

In conclusion, Negr1 plays essential roles in mood regulation, adult neurogenesis (both hippocampal and olfactory), and salivary secretion. The study of Negr1-deficient mouse models has provided insights into its functions in mood disorders, autism-related behaviors, and salivary gland physiology, highlighting its potential as a therapeutic target for these conditions.