Dusp16, a dual-specificity phosphatase, is involved in dephosphorylating both phosphotyrosine and phosphoserine/phosphothreonine residues. It is a c-Jun N-terminal kinase-specific phosphatase that negatively modulates the mitogen-activated protein kinases (MAPKs) signaling pathway, which is crucial in many cellular processes such as cell proliferation, apoptosis, and inflammation [3,4].

In cancer, Dusp16 has been found to promote chemoresistance. In nasopharyngeal, colorectal, gastric, and breast cancer cells, higher Dusp16 expression leads to increased resistance to chemotherapy-induced cell death. Mechanistically, it inhibits JNK and p38 activation, reducing BAX accumulation in mitochondria and thus apoptosis [1].

In acute lung injury, although the related paper was retracted, the initial study proposed that circRNA_0001679 could regulate Dusp16 through miR-338-3p, affecting apoptosis and pro-inflammatory cytokine production [2,5].

In non-alcoholic fatty liver disease (NAFLD), Dusp16 knockout in mice aggravated metabolic disorder, insulin resistance, and hepatic lipid accumulation and inflammation, as Dusp16 directly interacts with TAK1 and negatively regulates JNK signaling [4].

In Alzheimer's disease mouse models, suppressing Dusp16 overexpression induced by ELK1 promoted neural progenitor cell differentiation [6].

In summary, Dusp16 plays important roles in multiple biological processes and diseases. Gene knockout (KO) mouse models have revealed its significance in cancer chemoresistance, NAFLD, and neural differentiation in Alzheimer's disease, highlighting its potential as a therapeutic target for these disease areas.