CAMK2B (calcium/calmodulin-dependent protein kinase II beta) is a multifunctional serine/threonine kinase with distinct roles in neuronal and non-neuronal tissues. In neurons, CAMK2B functions both as a kinase and through kinase-independent structural mechanisms. It plays an essential role in dendritic spine and synapse formation by binding and bundling actin filaments, thereby enabling proper targeting of CAMK2A and supporting long-term potentiation and hippocampus-dependent learning 1. CAMK2B regulates neuronal migration and dendritic arborization during brain development 1. In skeletal muscle, CAMK2B modulates sarcoplasmic reticulum calcium transport and responds to exercise through phosphorylation of regulatory proteins including phospholamban and triadin 2. Under endoplasmic reticulum stress, CAMK2B phosphorylates the reticulophagy regulator RETREG1, enhancing ER autophagy 3. Dysregulation of CAMK2B is implicated in disease pathogenesis: de novo CAMK2B mutations cause intellectual disability through altered autophosphorylation affecting neuronal migration 1, while CAMK2B upregulation contributes to polycystic ovary syndrome by disrupting oocyte-granulosa cell communication 4. In glioma, CAMK2B suppresses tumor progression by inhibiting the Ras/Raf/MEK/ERK pathway 5. TDP-43 dysfunction in Alzheimer's disease leads to CAMK2B cryptic splicing accumulation 6.