{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRGS14 is a multifunctional scaffolding protein prominently expressed in hippocampal CA2 pyramidal neurons where it plays a critical role in governing synaptic plasticity and, consequently, learning and memory. In CA2, RGS14 naturally suppresses conventional long‐term potentiation (LTP) and promotes forms of long‐term depression (mGluR‐LTD) by limiting calcium influx into dendritic spines and modulating key downstream effectors such as CaMKII and ERK/MAP kinase. These actions help tune hippocampal-dependent and social cognitive processes and are associated with dynamic changes in protein expression during postnatal development, as well as a distinct CA2 proteome that underlies the unique physiology of this hippocampal subregion."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, RGS14 functions both as a GTPase-activating protein (GAP) for Gα_i/o subunits and as a guanine nucleotide dissociation inhibitor (GDI), displaying notable selectivity (e.g., effectively regulating Gα_i1 and Gα_i3 but not Gα_i2 unless modified). In addition, RGS14 contains tandem Ras/Rap binding domains that enable it to interact with active H-Ras as well as with Ca²⁺/calmodulin and other signaling molecules. Its dynamic interactions with partners such as Ric-8A further illustrate its role in integrating and modulating both receptor-dependent and receptor-independent G protein signaling pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in neuronal signaling, disruption or alteration of RGS14 expression has broad physiological implications. For example, reduced RGS14 function can lead to enhanced mitochondrial performance, increased brown adipose tissue, and improved metabolic and healthful aging profiles, while in the context of opioid receptor signaling, RGS14 modulates receptor phosphorylation and desensitization. Moreover, its influence on locomotor reactivity and protection against seizure-induced pathology underscores a wider impact on stress responses and cellular resilience, extending its importance well beyond synaptic regulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sarah Emerson Lee, Stephen B Simons, Scott A Heldt, et al. 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