{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DUSP22 (also known as JKAP or LMW‐DSP2) is a dual‐specificity phosphatase that plays diverse roles in regulating key signaling pathways across several disease contexts. In T‐cell lymphomas—including anaplastic large cell lymphoma (ALCL) and other peripheral T‐cell lymphomas—recurrent chromosomal rearrangements disrupting DUSP22 result in its down‐regulation, a change that correlates with distinct clinical outcomes; notably, DUSP22‐rearranged cases tend to have a more favorable prognosis compared to other genetic subtypes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " Functional studies in malignant T cells have further demonstrated that restoring DUSP22 expression can suppress cellular expansion, induce apoptosis, and reduce clonogenicity and tumorigenicity, thereby underscoring its tumor suppressor role."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond lymphoid malignancies, epigenetic silencing of DUSP22 via promoter hypermethylation has been identified in the hippocampus of Alzheimer’s disease patients, where reduced DUSP22 activity leads to diminished inhibition of protein kinase A (PKA) and thereby affects TAU phosphorylation and CREB signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In estrogen receptor–positive breast cancer cells, β‑estradiol induces DUSP22 mRNA expression, and elevated DUSP22 levels act as a negative regulator of ERα‐mediated signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Similarly, in systemic lupus erythematosus (SLE), decreased DUSP22 expression in peripheral blood T cells correlates with hyperactivation of these cells and is associated with adverse renal outcomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the setting of solid tumors, reduced DUSP22 expression has been observed in colorectal and prostate cancers, where its loss is linked to enhanced tumor cell proliferation and poorer progression‐free or disease‐free survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Moreover, studies on the murine homolog JKAP indicate that DUSP22 is required for optimal activation of the JNK pathway in response to pro‐inflammatory stimuli."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings highlight DUSP22 as a critical modulator of signal transduction pathways that control cell survival, proliferation, differentiation, and apoptosis in both oncogenic and non‐oncogenic settings. Its varied roles in T-cell regulation, neurodegeneration, hormone response, and tumor suppression underscore DUSP22’s potential as both a biomarker and a therapeutic target across a range of diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Edgardo R Parrilla Castellar, Elaine S Jaffe, Jonathan W Said, et al. 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