CREB (cAMP response element-binding protein) is a well-known transcription factor that plays a pivotal role in the regulation of gene expression in response to various stimuli, including neuronal activity, hormones, and growth factors. Phosphorylation of CREB at serine 133 (Ser133) is a critical event for its activation, as it enhances the binding of CREB to the cAMP response element (CRE), leading to the transcription of target genes involved in processes such as learning, memory, and cell survival. The phosphorylation of CREB at Ser133 is typically catalyzed by various protein kinases, including protein kinase A (PKA), calcium/calmodulin-dependent protein kinase IV (CaMKIV), and mitogen-activated protein kinase (MAPK). This phosphorylation event is a robust indicator of neuronal activation and synaptic plasticity, making it a widely studied marker in neurobiological research.