Leucine-rich repeat-containing protein 4C (NGL-1) (NGL-1)

NGL-1 (Netrin-G1 ligand), also known as LRRC4C, is a transmembrane protein belonging to the leucine-rich repeat (LRR) family that serves as a key synaptic adhesion molecule [UniProt, https://www.uniprot.org/uniprotkb/Q969U0/entry]. It is primarily recognized for its role in the central nervous system, where it acts as a postsynaptic receptor for the presynaptic ligand Netrin-G1 to promote the development and maintenance of excitatory synapses [PubMed, https://pubmed.ncbi.nlm.nih.gov/14595443/]. Beyond its neurobiological functions, NGL-1 has been identified as a critical player in the tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) [NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11102144/]. In this context, NGL-1 is expressed by cancer-associated fibroblasts and immune cells, contributing to an immunosuppressive environment and supporting tumor growth through metabolic and signaling pathways [AACR, https://aacrjournals.org/cancerres/article/82/22_Supplement/PR017/710685/Abstract-PR017-Stromal-Netrin-G1-ligand-NGL-1-A]. Research indicates that disrupting the NGL-1/Netrin-G1 axis using experimental peptides can reduce tumor progression and improve response to chemotherapy, making it a promising target for cancer immunotherapy [bioRxiv, https://www.biorxiv.org/content/10.1101/2024.05.15.594354v1]. However, because of its essential role in brain function, therapeutic interventions must carefully consider potential neurological side effects, such as those observed in neurodevelopmental disorders like autism and schizophrenia [PubMed, https://pubmed.ncbi.nlm.nih.gov/31649508/].

Other names

LRRC4CNetrin-G1 ligandNGL1KIAA1580

Antagonism of the Netrin-G1/NGL-1 interaction to modulate the tumor microenvironment and restore anti-tumor immune activity.