Dusp16, a dual-specificity phosphatase, is known for its role in dephosphorylating both phosphotyrosine and phosphoserine/phosphothreonine residues. It is involved in negatively modulating the mitogen-activated protein kinases (MAPKs) signaling, especially regulating JNK and p38 pathways [2,3]. This regulation has implications in multiple biological processes and disease conditions. Genetic models, such as gene knockout (KO) models, are valuable tools for studying its functions.

In cancer research, Dusp16 has been implicated in chemoresistance. In nasopharyngeal, colorectal, gastric, and breast cancer cells, those with higher Dusp16 expression are more resistant to chemotherapy-induced cell death. Knockdown of Dusp16 in cancer cells increases their sensitivity to treatment, as Dusp16 inhibits JNK and p38 activation, reducing BAX accumulation in mitochondria and thus apoptosis [1].

In non-alcoholic fatty liver disease (NAFLD), Dusp16 knockout in high-fat diet-challenged mice significantly aggravated metabolic disorder, insulin resistance, hepatic lipid accumulation, and inflammation, as Dusp16 directly interacts with TAK1 and negatively regulates JNK signaling [3].

In Alzheimer's disease mouse models, increased Dusp16 expression was detected, and silencing Dusp16 promoted neural progenitor cell differentiation, synaptic transmission, and cognitive benefits [4].

In conclusion, Dusp16 plays crucial roles in cancer chemoresistance, NAFLD, and neural differentiation in Alzheimer's disease. Gene knockout models have been instrumental in revealing these functions, providing insights into the underlying molecular mechanisms and potential therapeutic targets for these diseases.