{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRGS2 is emerging as a critical modulator of G‐protein–coupled receptor signaling with a central role in cardiovascular and respiratory physiology. Acting as a GTPase‐activating protein (GAP), RGS2 preferentially attenuates Gαq‐mediated pathways, thereby fine‐tuning vasoconstrictor responses, regulating adenylyl cyclase activity and ultimately contributing to blood pressure homeostasis. In vascular smooth muscle, reduced RGS2 expression or mutations that enhance its degradation via N‐end rule pathways have been linked to hypertension and preeclamptic phenotypes, while in airway smooth muscle RGS2 induction by combination glucocorticoid/long‐acting β₂‐agonist treatments mediates bronchoprotection by dampening Ca²⁺ mobilization in response to contractile stimuli."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its vascular actions, RGS2 plays a significant role in neural signaling and behavioral regulation. Variations in the RGS2 gene and altered expression levels have been associated with anxiety disorders, panic and posttraumatic stress disorder, as well as with adverse motor side‐effects from antipsychotic drugs. By modulating receptor–effector coupling in dopaminergic and adrenergic systems, RGS2 contributes to the fine tuning of neuronal responsiveness that underlies stress‐related and affective phenotypes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "23"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of cancer biology, RGS2 appears to function as a tumor suppressor. Numerous studies have reported that downregulation—often through epigenetic mechanisms—of RGS2 is common in breast, colorectal, ovarian, and bladder cancers. Loss of RGS2 expression correlates with enhanced growth, increased transformation potential, and poorer clinical outcome, while restoration of its expression suppresses oncogenic signaling and proliferation. Such findings have raised the prospect of RGS2 serving as both a prognostic biomarker and a target for therapeutic intervention in malignancies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "24", "end_ref": "32"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, RGS2 integrates diverse signal transduction pathways through direct protein–protein interactions and post‐translational modifications. It directly associates with specific GPCRs and scaffolding partners (such as spinophilin), modulates adenylyl cyclase and Ca²⁺ channel activity, and is itself subject to precise regulation by processes including N‑terminal acetylation and proteasomal degradation. Epigenetic modifications further control RGS2 expression, linking its dysregulation not only to altered receptor signaling in cellular homeostasis but also to cognitive deficits observed in neurodegenerative diseases. Collectively, these multifaceted interactions underscore the role of RGS2 as a pivotal hub orchestrating the cellular response to extracellular stimuli."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "33", "end_ref": "41"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Samina Salim, Srikumar Sinnarajah, John H Kehrl, et al. 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