Dusp5, a member of the serine-threonine phosphatase family, belongs to the dual-specificity phosphatases (DUSPs) superfamily. It can dephosphorylate extracellular regulated protein kinases (ERK), and is involved in modulating metabolic signals, inflammatory responses, and cancer progression. It plays crucial roles in multiple signaling pathway transductions, such as the TGF-β/Smad and NF-κB pathways, and is associated with various diseases including kidney diseases, osteoporosis, lung adenocarcinoma, osteoarthritis, and viral infections [1-8].

In acute kidney injury (AKI), Dusp5 deficiency suppresses disease progression by enhancing autophagy through the AMPK/ULK1 pathway. Knockdown of Dusp5 attenuates the production of inflammatory factors and apoptotic cells in renal tubular epithelial cells [1]. In osteogenic differentiation, Dusp5 promotes it in mesenchymal stromal cells (MSCs) by activating the SMAD1 signaling pathway [2]. In lung adenocarcinoma, knockdown of Dusp5 suppresses epithelial-mesenchymal transition (EMT), migration, invasion, and reverses EGFR-TKI resistance via the TGF-β/Smad signaling pathway [3]. In osteoarthritis, Dusp5 suppresses interleukin-1β-induced chondrocyte inflammation by inhibiting the NF-κB and ERK signaling pathways [4]. Against dengue virus infection, overexpression of Dusp5 inhibits viral replication by suppressing F-actin rearrangement [5]. In BCG-infected RAW264.7 cells, Dusp5 suppresses autophagy via the ERK1/2 signaling pathway [6]. In pulmonary hypertension, Dusp5-mediated inhibition of smooth muscle cell proliferation suppresses the disease and right ventricular hypertrophy [7]. In fish infected with Singapore grouper iridovirus, overexpression of Dusp5 inhibits viral infection by regulating immune-related factors [8].

In conclusion, Dusp5 is a key regulator involved in multiple biological processes and disease conditions. Studies using gene knockout or knockdown models have revealed its diverse functions, such as in inflammation regulation, autophagy modulation, and disease progression control in areas like kidney, bone, cancer, and viral infections. These findings provide potential therapeutic targets for related diseases.