CAMK2A is a calcium/calmodulin-dependent protein kinase that functions as a central regulator of synaptic plasticity and neuronal development. Upon Ca2+/calmodulin binding and autophosphorylation, CAMK2A autonomously regulates long-term potentiation, synaptic transmission, and dendritic spine development 12. The kinase is essential for proper neuronal migration during brain development, with mutations affecting CAMK2A autophosphorylation at Thr286 impairing this process 3. Beyond synaptic functions, CAMK2A participates in interferon signaling, phosphorylating STAT1 in response to IFN-gamma stimulation to activate JAK-STAT pathways and promote ferroptosis inhibition 45. Clinically, de novo CAMK2A mutations cause intellectual disability and neurodevelopmental disorders, establishing the kinase's critical role in human brain function 3. CAMK2A dysfunction contributes to cardiac pathology through O-GlcNAcylation-mediated metabolic memory in diabetes, driving endothelial secretion of pathogenic extracellular vesicles that damage cardiomyocytes 6. Additionally, CAMK2A expression in hippocampal neurons modulates pain-related anxiety and depression through excitatory synaptic transmission to prefrontal corticotropin-releasing hormone neurons 7. Gene therapy approaches exploiting CAMK2A promoter specificity show promise for treating focal cortical dysplasia-related seizures 8, and CAMK2A stabilization participates in pathological macrophage polarization in smoking-induced emphysema 9.