Dusp18, a dual-specificity phosphatase, belongs to the protein tyrosine phosphatase family. It can dephosphorylate both phospho-tyrosyl and phospho-seryl/threonyl residues. Dusp18 is involved in multiple biological pathways, such as mitogenic signal transduction, cell cycle control, and various disease-related processes [4,5].

In a mouse model of colorectal cancer, inhibition of Dusp18 impairs cholesterol biosynthesis and promotes anti-tumor immunity. Dusp18 dephosphorylates and stabilizes USF1, which induces SREBF2, allowing cells to accumulate lanosterol and release it into the tumor microenvironment. Lanosterol uptake by CD8+ T cells suppresses their activation, and Dusp18 inhibition can enhance anti-tumor immunity [1].

In osteoclasts, Kisspeptin-10 binding to Gpr54 up-regulates Dusp18, which dephosphorylates Src at Tyr 416. Kiss1, Gpr54, and Dusp18 knockout mice all exhibit osteoclast hyperactivation and bone loss, indicating Dusp18's role in preventing bone loss [2].

In hepatocellular carcinoma cells, hypoxia-induced HIF1A activates Dusp18-mediated MAPK14 dephosphorylation, promoting cell migration and invasion [3].

In conclusion, Dusp18 plays essential roles in multiple biological processes and diseases. Mouse models with Dusp18 knockout or inhibition have revealed its functions in cancer immunity, bone metabolism, and cancer cell migration. Understanding Dusp18's functions through these models provides insights into potential therapeutic strategies for colorectal cancer, bone-loss-related diseases, and hepatocellular carcinoma.