CAMK2G encodes a calcium/calmodulin-dependent protein kinase that functions in both skeletal muscle and the central nervous system. In muscle, it regulates sarcoplasmic reticulum calcium transport and controls calcium release through phosphorylation of triadin in fast-twitch fibers. In neurons, CAMK2G promotes dendritic spine formation, synaptic plasticity, and long-term potentiation, and is essential for proper neurite outgrowth and arborization. The protein achieves autonomous activity following calcium/calmodulin binding and autophosphorylation. CAMK2G pathogenic variants are associated with neurodevelopmental disorders including intellectual disability, developmental delay, and behavioral problems 1. A de novo p.Arg292Pro mutation acts as a pathogenic gain-of-function, increasing phosphotransferase activity and impairing neuronal maturation 1. In cancer contexts, CAMK2G drives cisplatin resistance in ovarian cancer by sensing reactive oxygen species and regulating ITPKB phosphorylation to maintain redox homeostasis 2, while promoting neuronal differentiation and inhibiting migration in neuroblastoma 3. In myelofibrosis, CAMK2G acts as an effector in MPL-JAK2 signaling; CAMK2G inhibition with berbamine sensitizes resistant cells and improves survival in murine models 4. Recent evidence suggests CAMK2G inhibitors such as RA306 may target PEAK1-driven triple negative breast cancer through disruption of CAMK2 activation 5. CAMK2G expression also correlates with odontoblastic differentiation through TET1-mediated epigenetic regulation 6.