{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Calcium/calmodulin-dependent protein kinase type 1γ (CAMK1G) is emerging as a key mediator of calcium‐dependent intracellular signaling with diverse roles in neuronal development, synaptic plasticity, and neurodegeneration. At the molecular level, CAMK1G is activated by Ca²⁺/calmodulin binding and phosphorylation by upstream CaMKK, and its membrane localization is achieved via a prenylation‐dependent mechanism that targets it to specific lipid microdomains ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "]. Such precise spatial and temporal activation enables CAMK1G to regulate activity‐dependent dendritic arborization and synaptogenesis via pathways that include Rac signaling, thereby influencing neuronal morphology and synaptic efficacy ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "]."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, environmental stimuli and neurotoxicants modulate CAMK1G expression. Acute exposure to pyrethroid insecticides, for instance, leads to a dose‐dependent and splice variant–specific increase in CAMK1G mRNA in the frontal cortex, implicating it as part of an adaptive neurotoxic response ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "]. Altered CAMK1G transcript levels have also been reported under conditions of compromised neurotrophic support (e.g., following BDNF depletion) and prenatal ethanol exposure, suggesting that dysregulation of this kinase may contribute to deficits in neuronal survival and plasticity ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "]. Moreover, in models of Huntington’s disease, local deacetylation at gene promoters including CAMK1G has been associated with an increased vulnerability to transcriptional dysregulation ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "]."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond these cellular roles, genetic and systems‐based studies have linked CAMK1G to human disease. Genome‐wide association analysis in Han Chinese populations has identified CAMK1G as a susceptibility locus for amyotrophic lateral sclerosis ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "]. In parallel, network analyses in schizophrenia and inflammatory myositis have singled out CAMK1G as a hub gene associated with synaptic transmission and immune signaling, respectively ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "]. Finally, early fragment‐based screening efforts have yielded selective small molecules targeting CAMK1G, underscoring its potential as a therapeutic target ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "]. \n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies position CAMK1G as a multifaceted kinase that not only orchestrates calcium‐dependent neuronal signaling and structural plasticity but also participates in the pathogenesis of diverse neurodegenerative and neuroinflammatory disorders. As such, CAMK1G represents both a putative biomarker for disease susceptibility and a promising target for therapeutic intervention.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sayaka Takemoto-Kimura, Natsumi Ageta-Ishihara, Mio Nonaka, et al. 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