Transcription factors play a crucial role in long-term memory and synaptic plasticity. The review discusses the molecular mechanisms underlying these processes, focusing on families of transcription factors such as CREB, C/EBP, Egr, AP-1, and Rel. These factors regulate gene expression necessary for synaptic plasticity and memory formation. Transcription is a highly regulated process involving interactions between chromatin and proteins, with some essential for basal transcription and others for gene activation or repression. Evidence from gene expression studies, genetic mutations, and molecular inhibition shows that transcription is essential for memory formation. Transcription factors like CREB are involved in long-term synaptic plasticity and memory, with CREB-dependent gene expression being critical for long-term memory consolidation. CREB is activated by phosphorylation, particularly at Ser 133, and its activity is regulated by signaling pathways such as cAMP-PKA and MAPK. Studies in invertebrates like Aplysia and vertebrates like mice have shown that CREB is essential for long-term memory and synaptic plasticity. C/EBP family members also play a role in memory formation, with different isoforms having distinct functions. C/EBPβ and C/EBPδ are involved in memory consolidation and synaptic plasticity, with their expression regulated by signaling pathways. The review highlights the importance of transcription factors in regulating gene expression during memory formation and synaptic plasticity, emphasizing their role in the molecular signatures of long-term memory.Transcription factors play a crucial role in long-term memory and synaptic plasticity. The review discusses the molecular mechanisms underlying these processes, focusing on families of transcription factors such as CREB, C/EBP, Egr, AP-1, and Rel. These factors regulate gene expression necessary for synaptic plasticity and memory formation. Transcription is a highly regulated process involving interactions between chromatin and proteins, with some essential for basal transcription and others for gene activation or repression. Evidence from gene expression studies, genetic mutations, and molecular inhibition shows that transcription is essential for memory formation. Transcription factors like CREB are involved in long-term synaptic plasticity and memory, with CREB-dependent gene expression being critical for long-term memory consolidation. CREB is activated by phosphorylation, particularly at Ser 133, and its activity is regulated by signaling pathways such as cAMP-PKA and MAPK. Studies in invertebrates like Aplysia and vertebrates like mice have shown that CREB is essential for long-term memory and synaptic plasticity. C/EBP family members also play a role in memory formation, with different isoforms having distinct functions. C/EBPβ and C/EBPδ are involved in memory consolidation and synaptic plasticity, with their expression regulated by signaling pathways. The review highlights the importance of transcription factors in regulating gene expression during memory formation and synaptic plasticity, emphasizing their role in the molecular signatures of long-term memory.