{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DIRAS2 is a small Ras‐related GTPase that has emerged as a multifunctional signaling molecule with potential roles in both brain function and tumor biology. In the central nervous system, DIRAS2 is highly expressed in the hippocampus, cerebral cortex, and specific neuronal subtypes (especially glutamatergic and catecholaminergic neurons), and genetic as well as functional studies have implicated promoter polymorphisms that increase its expression in the pathophysiology of attention‐deficit/hyperactivity disorder by altering prefrontal response control and related cognitive functions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n At the molecular level, DIRAS2 (also referred to as Di‐Ras2) is characterized by a low intrinsic GTPase activity and rapid intrinsic nucleotide exchange. Biochemical studies demonstrate that it can form high‐affinity complexes with regulatory proteins such as SmgGDS, which in turn modulates its nucleotide binding and stability, suggesting that DIRAS2 partakes in distinct signaling pathways independent of classic Ras effector interactions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of cancer, DIRAS2 appears to have divergent roles. In clear cell renal cell carcinoma, it is upregulated in the absence of the von Hippel–Lindau protein, where it promotes cell proliferation, migration, and invasion via activation of downstream mitogen‐activated protein kinase cascades, suggesting an oncogenic function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n Conversely, in glioma samples, DIRAS2 is strongly downregulated, implying that alterations in its expression may contribute to tumor suppression or reflect different tumor biology in central nervous system neoplasms."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Additionally, DIRAS2 has been identified as part of a network of proteins interacting with Peroxiredoxin 1 in the context of nicotine‐associated oral lesions. Here, the modulation of DIRAS2 levels by nicotine may contribute to altered cellular stress responses and disease development."}, {"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 indicate that DIRAS2 functions as a signaling modulator with context‐dependent roles in neuronal regulation and cancer, warranting further research to elucidate the precise mechanistic pathways through which it influences cell fate, neurodevelopment, and tumorigenesis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Andreas Reif, T Trang Nguyen, Lena Weissflog, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DIRAS2 is associated with adult ADHD, related traits, and co-morbid disorders."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuropsychopharmacology (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/npp.2011.120"}], "href": "https://doi.org/10.1038/npp.2011.120"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21750579"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21750579"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Lena Grünewald, Elisabeth Toverud Landaas, Julia Geissler, et al. 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