Camk2d, encoding calcium/calmodulin-dependent protein kinase type 2 delta, is one of the major CAMK2 proteins expressed in the heart and early brain development. It is involved in calcium signaling pathways, which are crucial for normal physiological functions in both the heart and the nervous system [1,5].

In neurodevelopment, heterozygous variants in CAMK2D in humans are associated with intellectual disability, delayed speech, behavioral problems, and dilated cardiomyopathy. Gain-of-function variants seem to cause both neurological and cardiac issues, while loss-of-function variants may lead only to neurological symptoms, indicating its significant role in these processes [1].

In the heart, CAMK2D has been identified as a potential drug target for heart failure through genome-wide association and Mendelian randomization proteomics [3]. In addition, it serves as a molecular scaffold for the RNF8-MAD2 complex to induce the mitotic checkpoint in glioma [2]. In spermatogonia of experimental varicocele rats, silencing CAMK2D promotes their proliferation [4].

In conclusion, Camk2d is essential for normal heart and brain function. Studies on its variants in humans and functional changes in animal models like experimental varicocele rats have revealed its role in neurodevelopment, heart failure, mitotic regulation in glioma, and spermatogonia proliferation. These findings contribute to understanding the pathogenesis of related diseases and may provide new directions for therapeutic interventions.