Oxidative stress induced growth inhibitor 1 (OSGIN1), a tumor protein p53 (TP53)-target gene, is involved in the oxidative stress response. It has been implicated in various biological processes, such as apoptosis, ferroptosis regulation, and cell death control. The NFE2 like BZIP transcription factor 2 (NFE2L2)-dependent pathway also plays a role in its regulation [1].

In pancreatic ductal adenocarcinoma (PDAC) cells, genetic depletion of OSGIN1 promotes ferroptosis, while its re-expression rescues ferroptosis resistance in NFE2L2-knockout cells, both in vitro and in animal models. OSGIN1 interacts with glutamate-cysteine ligase modifier subunit (GCLM), enhancing glutathione production to mitigate oxidative stress [1].

In non-small cell lung cancer (NSCLC), OSGIN1 knockdown inhibits cell growth and patient-derived NSCLC tumor growth in vivo, and increases tubulin polymerization and gefitinib sensitivity. Mechanistically, OSGIN1 enhances DYRK1A-mediated TUBB3 phosphorylation, modulating microtubule dynamics [2].

In a mouse model of pancreatitis, pancreatic knockdown of Osgin1 by AAV-pan abolished the therapeutic effects of FXR activation on pancreatitis, indicating that Osgin1 is a crucial mediator in the FXR-mediated protection against pancreatitis [3].

In ovarian cancer, loss of the OSGIN1 gene promotes cancer growth and confers resistance to drug-induced ferroptosis, through activation of the AMPK-SLC2A3 axis [4].

In conclusion, OSGIN1 plays diverse and significant roles in multiple biological processes and diseases. Gene knockout models, such as in PDAC, NSCLC, pancreatitis, and ovarian cancer models, have revealed its importance in regulating ferroptosis, tumor growth, microtubule dynamics, and autophagy. These findings suggest that OSGIN1 could be a potential therapeutic target for these diseases.