Lgi3, also known as leucine-rich glioma inactivated 3, is a secreted protein-encoding gene. It belongs to the LGI/epitempin family. Functionally, it is involved in multiple biological processes. In the nervous system, it may be associated with synaptic transmission and plasticity, and in the skin, it is related to keratinocyte functions. Its associated pathways include those related to Akt phosphorylation, NF-κB activation, and others, which are crucial for various physiological activities [1-10].

In mice lacking Lgi3, the juxtaparanodal clustering of ADAM23 and Kv1 channels is disrupted, suppressing Kv1-channel-mediated short-term synaptic plasticity, indicating its importance in fine-tuning synaptic transmission [1,3]. In skin-related studies, LGI3 knockdown in HaCaT cells reduces cell migration and the expression of differentiation markers, showing its role in keratinocyte migration and differentiation [2,4]. In a murine model of atopic dermatitis, treatment with LGI3 peptide improves skin barrier function, suggesting its potential in treating skin barrier-related diseases [5].

In conclusion, Lgi3 plays essential biological functions in both the nervous system and skin. Gene-knockout mouse models have revealed its roles in regulating synaptic plasticity in the nervous system and keratinocyte-related functions in the skin, as well as its potential in treating atopic dermatitis. These findings contribute to understanding the molecular mechanisms of related diseases and provide potential therapeutic targets.