NLR family member X1 (NLRX1) (NLRX1)

Nucleotide-binding oligomerization domain, Leucine-rich Repeat containing X1 (NLRX1) is a mitochondrial-localized member of the NOD-like receptor family that serves as a pivotal negative regulator of the innate immune system [UniProt: Q86UT6]. Unlike most NLRs that promote inflammasome assembly, NLRX1 functions as an immune checkpoint by inhibiting pro-inflammatory pathways, including NF-kappaB and the RIG-I-MAVS signaling cascade [PubMed: 18345003]. It also plays a significant role in regulating mitochondrial reactive oxygen species (ROS) production and autophagy, thereby maintaining cellular homeostasis during stress [PubMed: 21441496]. Dysregulation of NLRX1 has been implicated in the pathogenesis of various inflammatory conditions, most notably inflammatory bowel disease (IBD), chronic obstructive pulmonary disease (COPD), and certain cancers where its loss leads to uncontrolled inflammation [PubMed: 25643613]. Current therapeutic development focuses on small-molecule agonists like NX-13, which are designed to activate NLRX1 in the gastrointestinal tract to induce mucosal healing and suppress cytokine production in patients with ulcerative colitis [ClinicalTrials.gov: NCT04834167]. By targeting this intracellular regulator, these therapies aim to provide potent anti-inflammatory effects while minimizing the risks associated with systemic immunosuppression.

Other names

NLR family member X1NOD-like receptor X1NOD9NOD26CLR11.3Nucleotide-binding oligomerization domain protein 9

Agonism of NLRX1 to suppress pro-inflammatory signaling pathways and promote mucosal healing.