Fndc3b, fibronectin type III domain-containing protein 3B, is an important regulator of metabolism. It has been associated with multiple biological pathways, and its dysregulation is linked to various diseases. Understanding its function through genetic models like gene knockout (KO) or conditional knockout (CKO) mouse models can provide insights into its role in normal biology and disease [1].

In alcoholic fatty liver disease, hepatocyte-specific Fndc3b knockdown in mice aggravated alcohol-induced liver steatosis via AMP-activated protein kinase (AMPK) inhibition. Also, Fndc3b deletion significantly exacerbated ethanol-mediated lipid peroxidation, and its inhibition-mediated AMPK inactivation was associated with iron overload and ferroptosis. This shows Fndc3b's role in preventing hepatic steatosis and ferroptosis in response to chronic alcohol consumption [1].

In cervical cancer, analysis of databases indicated that increased Fndc3b expression was correlated with lower overall survival, and co-expression network analysis suggested its role in cancer development via ER stress, UPR, cell migration and invasion [2].

In gastric cancer, a novel protein FNDC3B-267aa encoded by circ0003692, a circRNA derived from Fndc3b, inhibited gastric cancer migration by promoting proteasomal degradation of c-Myc [3].

In conclusion, Fndc3b plays crucial roles in metabolism-related processes and disease development. The KO/CKO mouse models have been instrumental in revealing its functions in alcoholic fatty liver disease. In addition, in various cancers such as cervical, gastric, and others, studies have shown its potential oncogenic or tumor-suppressive roles, highlighting its importance as a potential therapeutic target in these disease areas.