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Insulin-like Growth Factor IGF-II is emerging as a critical factor in synaptic plasticity and memory function. IGF-II is abundantly expressed in the central nervous system. IGF-II expression and function in the brain are mediated by intricate processes through the IGF-II receptor, which are highly expressed in neurons, and have a crucial role in regulating protein trafficking, synthesis and degradation. IGF-II deficiencies within the brain, serum, or cerebrospinal fluid are associated with various neurological disorders, including Alzheimer’s, Parkinson’s, depression and anxiety. Elevating IGF-II levels has demonstrated positive outcomes, enhancing memory and alleviating symptoms in age-related and neurodegenerative conditions.