Understanding the pathogenetic mechanisms underlying altered neuronal function associated with CAMK2B mutations

'Dominant mutations in CAMK2B, encoding a subunit of the calcium/calmodulin-dependent protein kinase II (CAMK2), a serine/threonine kinase playing a key role in synaptic plasticity, learning and memory, underlie a recently characterized neurodevelopmental disorder (MRD54) characterized by delayed psychomotor development, mild to severe intellectual disability, hypotonia, and behavioral abnormalities. Targeted therapies to treat MRD54 are currently unavailable. In this review, we revise current knowledge on the molecular and cellular mechanisms underlying the altered neuronal function associated with defective CAMKIIβ function. We also summarize the identified genotype-phenotype correlations and discuss the disease models that have been generated to profile the altered neuronal phenotype and understand the pathophysiology of this disease.