Neuroligin 4 (NLGN4) (NLGN4)

Neuroligin 4 (NLGN4) is a cell surface adhesion molecule traditionally recognized for its role in the central nervous system, where it facilitates synapse formation and maintenance by interacting with neurexins. Recent research, notably by Dr. Rifaat Safadi, has identified NLGN4 as a novel immunomodulatory checkpoint in the liver, where it is overexpressed on Natural Killer (NK) cells in the context of Non-Alcoholic Steatohepatitis (NASH) and advanced fibrosis. This overexpression inhibits the NK cells' ability to eliminate activated hepatic stellate cells, the primary drivers of liver scarring. Therapeutic strategies, such as the drug candidate BL-1210 and the peptide Luji-4, aim to inhibit NLGN4 or its interaction with Neurexin 1-beta to restore the anti-fibrotic propensity of NK cells. This target represents a pioneering approach to treating metabolic liver diseases by leveraging the innate immune system to resolve fibrosis and prevent progression to cirrhosis.

Other names

NLGN4XNLGN4YNeuroligin-4NGn4NLGn4Neuroligin 4, X-linkedNeuroligin 4, Y-linked

Inhibition of NLGN4 expression or the NLGN4-Neurexin 1-beta (NRXN1b) protein-protein interaction to restore and enhance the anti-fibrotic activity of Natural Killer (NK) cells against activated hepatic stellate cells.