Tnip2, also known as ABIN2, is a negative regulator of NF-κB signaling. It can bind A20 to suppress inflammatory cytokines-induced NF-κB activation, thus inhibiting inflammatory response and apoptosis. It is also involved in RNA metabolism [1,4,5]. The NF-κB signaling pathway, in which Tnip2 is implicated, is pivotal in controlling cellular responses to environmental stresses, and abnormal NF-κB signaling is seen in many autoimmune diseases and cancers [5].

In an in vitro study, TNIP2 overexpression decreased the protein levels of β -secretase (BACE1) and C99, as well as Aβ peptides in cell models stably expressing human full-length APP695, suggesting it inhibits amyloidogenic processing by regulating the 3'UTR-associated mRNA decay of BACE1, which is critically associated with Alzheimer's disease (AD) [1].

In patients with major depressive disorder (MDD), the mRNA expressions of TNIP2 were significantly higher in monocytes, and its level was positively correlated with the severity of depression. Overexpression of GRβ promotes the mRNA levels of TNIP2 and TNF-α in human monocytes, indicating the activation of GRβ/TNIP2/TNF-α axis may induce inflammation in MDD patients [2].

In pulmonary arterial hypertension (PAH), a novel missense variant in the TNIP2 gene was discovered in affected individuals. The knockdown of TNIP2 increased NF-κB activity in healthy lung pericytes, correlating with increased proliferation, suggesting loss of function in TNIP2 promotes pulmonary vascular remodeling [3].

In rats with spinal cord injury (SCI), TNIP2 expression was increased during SCI, and its overexpression inhibited M1 polarization and pro-inflammatory cytokine production in microglia, protecting against inflammatory responses [4].

In hyperoxia-induced bronchopulmonary dysplasia-like inflammation, TNIP2, as a direct target of miR34a, negatively regulated activation of NLRP3 inflammasome and the production of IL-1β. Overexpressing TNIP2 ameliorated hyperoxia-induced production of IL-1β and cell apoptosis, suggesting it may be a potential clinical marker in the diagnosis of BPD [6].

In multiple organ dysfunction syndrome (MODS) following severe trauma, TNIP2 was significantly decreased, and administration of TNIP2-plasmid inhibited the inflammation response and oxidative stress by preventing NF-κB activation, playing a protective role in MODS development [7].

In osteoarthritis (OA), patients showed downregulation of TNIP2. Overexpression of miR-8082 inhibitor promoted cell proliferation, inhibited apoptosis, and released inflammatory cytokines in LPS-treated chondrocytes, and silencing of TNIP2 reversed these effects, indicating NAV2-AS5 relieves chondrocyte inflammation by targeting miR-8082/TNIP2 in OA [8].

In conclusion, Tnip2 is crucial in regulating inflammatory responses, as revealed through various model-based research. Its role in diseases such as AD, MDD, PAH, SCI, BPD, MODS, and OA has been demonstrated. These findings from different disease models contribute to understanding the molecular mechanisms of these diseases and may provide potential therapeutic targets.