Figure 3: TXNIP overexpression and deregulation of cellular processes. TXNIP is known to express and/or translocate to various organelles under stress including the cytosol (and ER), mitochondria (MT), nucleus and plasma membrane. Similarly, Trx1 is present in the cytosol and nucleus while Trx2 is the mitochondrial isoform. Inhibition of Trx1 and Trx2 by TXNIP releases ASK1 (1) from ER and ASK2 from MT, respectively, and induces apoptosis. (2) In addition, damaged/depolarized mitochondrial release ROS, which is critical for NLRP3 inflammasome assembly and inflammation. (3) In the nucleus, TXNIP releases JAB1 from p27kip1 binding via trapping Trx1 and prevents p27kip1 degradation. P27kip1 is a cyclin-dependent protein kinase CDK4/6 inhibitor, and mediates G0/G1 cell cycle arrest. (4) Furthermore, translocation of TXNIP to the plasma membrane causes VEGF-R2 stabilization, VEGF-A signaling, and EC proliferation. This process may enhance retinal capillary neovascularization. (5) Lastly, TXNIP causes insulin resistance by trapping glucose transporters glut 1 and glut 4 (or neuronal glut 3) containing vesicles in the cytosol. Therefore, prolonged TXNIP up-regulation in diabetic retinopathy will have deleterious effects in organelle function and cell viability.