Lanthionine synthetase C-like protein (LANCL) (LANCL)

Lanthionine synthetase C-like (LANCL) proteins are a family of eukaryotic proteins, including LANCL1, LANCL2, and LANCL3, that are homologous to bacterial lanthionine synthetase C enzymes. LANCL2 has gained significant attention as a therapeutic target for autoimmune, inflammatory, and metabolic diseases due to its role as a novel receptor that regulates immunometabolic signaling. Activation of LANCL2 by natural ligands like abscisic acid or synthetic agonists such as omilancor (BT-11) promotes the stability of regulatory T cells (Tregs) and suppresses the production of pro-inflammatory cytokines, thereby restoring immune homeostasis. This mechanism involves the activation of the AMPK and mTORC2/Akt pathways, which are critical for maintaining cellular energy balance and metabolic health. LANCL1 is primarily expressed in the brain and is involved in antioxidant defense and neuronal protection, while also showing emerging roles in cancer progression. Therapeutic candidates targeting the LANCL2 pathway are currently in clinical development for conditions such as ulcerative colitis, Crohn's disease, and systemic lupus erythematosus, demonstrating a favorable safety profile with minimal systemic immunosuppression.

Other names

LANCL1LANCL2LANCL3GPR69AGPR69Bp40TASPLanC like 1LanC like 2Lanthionine synthetase component C-like protein

LANCL2 agonists activate the LANCL2-mediated immunometabolic pathway, which enhances the stability and suppressive function of regulatory T cells (Tregs) while downregulating pro-inflammatory effector T cell responses and cytokine production (e.g., TNF-alpha, MCP-1). This activation also modulates cellular metabolism through the AMPK and mTORC2/Akt pathways, promoting mitochondrial oxidative phosphorylation and glucose uptake.