Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 3 (LINGO3)

Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 3 (LINGO3) is an orphan transmembrane protein in the immunoglobulin superfamily, containing leucine-rich repeat and Ig-like domains. LINGO3 is expressed in a variety of tissues, including the intestinal and airway epithelium, the central nervous system, and during development. In the intestine, LINGO3 is specifically expressed in enterocytes and at the base of crypts within the intestinal stem cell niche, where it is essential for tissue regeneration following injury and for the activity of intestinal stem cells, as demonstrated in models of inflammatory colitis. LINGO3 interacts with key signaling pathways such as MAPK/ERK and STAT3 during mucosal healing, though no high-affinity ligand is known and it is considered an orphan receptor. Beyond gut biology, LINGO3 is implicated in processes of nervous system development, neurodegeneration, tumorigenesis, and stress-related psychiatric conditions, likely through interaction with related LINGO family proteins and modulation of cellular signaling complexes. Its deficiency leads to loss of stem cell function, improper tissue architecture, increased apoptosis, and reduced proliferation after tissue injury.

Other names

LERN2LRRN6BLeucine-rich repeat neuronal protein 2Leucine-rich repeat neuronal protein 6BLeucine rich repeat neuronal 6B

Not fully established; TFF2-Fc therapeutic effect in colitis requires LINGO3 for activation of MAPK/ERK signaling, but direct high-affinity ligand interaction has not been confirmed