NLRX1, NLR family member X1, is a unique pattern recognition molecule in the Nod-like receptor (NLR) family. It localizes to the mitochondrial matrix in resting conditions and is involved in multiple cellular processes such as antiviral immunity, apoptosis, ROS generation, mitochondrial metabolism, and mitophagy. It can regulate signaling pathways like type-I interferon, NF-κB, and is associated with various diseases [2,3,4]. Genetic models, especially knockout models, are valuable for studying its functions.

In the context of intervertebral disc degeneration (IDD), NLRX1 loss is linked to nucleus pulposus (NP) cell senescence and IDD progression due to disordered mitochondrial quality. NLRX1 can couple mitochondrial dynamic factors and mitophagy activity to maintain mitochondrial quality. Its absence leads to mitochondrial collapse, excessive mitophagy, and NP cell senescence. Mechanistically, it interacts with SLC39A7 to modulate mitochondrial Zn²⁺ trafficking [1]. In chronic obstructive nephropathy, NLRX1 knockout in mice led to enhanced M2 macrophage polarization, increased TGFβ secretion, and excessive renal fibrosis, indicating its role in preventing such pathological changes [5].

In conclusion, NLRX1 plays essential roles in maintaining mitochondrial function, regulating immune-related responses, and influencing disease-associated cellular processes. Studies using NLRX1 KO mouse models have revealed its significance in diseases like IDD and chronic obstructive nephropathy, providing insights into potential therapeutic strategies targeting NLRX1 for these conditions.