DUSP4 (dual specificity phosphatase 4) is a negative regulator of mitogen-activated protein kinase (MAPK) signaling that dephosphorylates both threonine and tyrosine residues on ERK1/2, JNK, and p38 kinases 1. Beyond canonical MAPK regulation, DUSP4 modulates additional signaling pathways; it dephosphorylates HSP90β to stabilize JAK1/2-STAT3 signaling in esophageal squamous cell carcinoma 2, and regulates ferroptosis through YTHDC1-mediated control of ferritin mRNA localization in hepatocellular carcinoma 3. DUSP4 expression is frequently dysregulated in multiple cancers. High DUSP4 expression correlates with worse prognosis in pancreatic ductal adenocarcinoma 4 and esophageal squamous cell carcinoma 2. In cancer therapeutics, DUSP4 loss paradoxically promotes drug resistance: DUSP4 deficiency mediates lenvatinib resistance through ERK pathway activation 5, while dual inhibition of DUSP4 and its paralog DUSP6 selectively impairs NRAS/BRAF mutant cell growth and resensitizes therapy-resistant cells 6. DUSP4 is regulated transcriptionally by cancer-associated factors including STAT3, YY1, CTCF, and FOXA1 1, and its protein stability is controlled by ubiquitination-mediated degradation 7. Beyond cancer, DUSP4 is overexpressed in systemic lupus erythematosus T cells, contributing to autoimmune pathology 8.