Dusp16, a dual-specificity phosphatase, is known to negatively modulate the mitogen-activated protein kinases (MAPKs) signaling, especially acting as a c-Jun N-terminal kinase (JNK)-specific phosphatase [3]. It is involved in multiple biological processes and diseases, playing a significant role in regulating cell fate-related pathways [1,2,3,4]. Genetic models are valuable for studying its functions.

In cancer, Dusp16 promotes chemoresistance in nasopharyngeal, colorectal, gastric, and breast cancer. Knockdown of Dusp16 in cancer cells increases their sensitivity to chemotherapy-induced cell death, as it inhibits JNK and p38 activation, reducing BAX accumulation in mitochondria and thus apoptosis [1]. In hepatocytes, Dusp16 knockout in high-fat diet-challenged mice exacerbates metabolic disorder, insulin resistance, lipid deposition, and inflammatory response by accelerating the activation of JNK, TAK1, and NF-κB signaling pathways [3]. In Alzheimer's disease mouse models, increased Dusp16 expression is detected, and its silencing promotes neural progenitor cell differentiation, synaptic transmission, and cognitive benefits, and it is involved in this process through regulating JNK phosphorylation and SOX2 expression [4].

In conclusion, Dusp16 is a key regulator in multiple biological processes and disease conditions. Through gene-knockout models, its role in cancer chemoresistance, hepatic dyslipidemia, and Alzheimer's disease-related neural differentiation has been revealed. Understanding Dusp16 functions helps in developing potential therapeutic strategies for these diseases.