Camk2a, short for Calcium/Calmodulin dependent protein kinase II alpha, is a key calcium signaling molecule in the glutamatergic signaling pathway [3,5]. It is activated by exogenous and endogenous stimuli, playing essential roles in multiple cell functions such as neuronal function, neurodevelopment, and cell plasticity [1,6].

In human studies, de novo mutations in Camk2a have been linked to intellectual disability, highlighting its importance in human brain function [1]. In mouse models, Camk2a knockout leads to learning and plasticity deficits, which can be rescued by adult expression of the gene, suggesting it doesn't have a critical irreversible role in neurodevelopment [6].

In the context of diseases, Camk2a has been implicated in various conditions. For example, in smoking-induced emphysema, circADAMTS6 stabilizes Camk2a mRNA to drive M2 macrophage polarization [2]. In lung adenocarcinoma, Camk2a supports tumor-initiating cells by upregulating SOX2 through EZH2 phosphorylation [3]. It also suppresses denervated muscle atrophy by maintaining Ca2+ homeostasis in muscle cells [4].

In conclusion, Camk2a is crucial for normal neuronal function, neurodevelopment, and cognitive ability. Its dysregulation is associated with intellectual disability, smoking-induced emphysema, lung adenocarcinoma, and denervated muscle atrophy. Mouse models, especially knockout models, have been instrumental in uncovering its role in these biological processes and disease conditions, providing potential therapeutic targets for related diseases.