| CYFIP2 — Cytoplasmic FMRP Interacting Protein 2 | |
|---|---|
| Symbol | CYFIP2 |
| Full Name | Cytoplasmic FMRP Interacting Protein 2 |
| Chromosome | 5q33.3 |
| NCBI Gene | 26999 |
| Ensembl | ENSG00000155189 |
| OMIM | 605322 |
| UniProt | Q9Y2D89 |
| Protein Class | FMRP Interacting Protein family |
| Molecular Weight | 125 kDa |
| Expression | Brain, [Neurons](/entities/neurons), [Cortex](/brain-regions/cortex), [Hippocampus](/brain-regions/hippocampus) |
CYFIP2 (Cytoplasmic FMRP Interacting Protein 2), also known as p155, is a critical neuronal protein that functions as a key regulator of synaptic plasticity, actin cytoskeleton dynamics, and RNA processing[1][2]. The protein is encoded by the CYFIP2 gene located on chromosome 5q33.3 and is highly expressed in the brain, particularly in the cerebral cortex and hippocampus — regions critically involved in learning, memory, and neurodegenerative processes[3].
CYFIP2 was originally identified as an interactor of FMR1 (Fragile X Mental Retardation 1), the gene mutated in Fragile X syndrome, linking it to synaptic dysfunction and neurodevelopmental disorders. However, emerging research has revealed important roles for CYFIP2 in neurodegenerative diseases including Alzheimer's Disease (AD) and Parkinson's Disease (PD)[4].
CYFIP2 contains several functional domains that mediate its diverse cellular functions:
The protein adopts a horseshoe-like structure that enables simultaneous binding to multiple partners, positioning it as a molecular scaffold coordinating signaling pathways at the synapse.
CYFIP2 plays multiple essential roles in neuronal physiology:
CYFIP2 is a key modulator of synaptic plasticity — the cellular basis of learning and memory. It regulates both excitatory and inhibitory synaptic transmission through its interactions with FMRP and the WAVE complex[5]. By controlling actin cytoskeleton dynamics at dendritic spines, CYFIP2 influences spine morphology, size, and stability — all critical parameters for proper synaptic connectivity.
As an FMRP-interacting protein, CYFIP2 participates in the regulation of mRNA translation at synapses. This function is particularly important for local protein synthesis required during long-term potentiation (LTP) and long-term depression (LTD), forms of synaptic plasticity underlying learning and memory[6].
During brain development, CYFIP2 regulates neuronal migration, axon guidance, and dendrite morphogenesis through its effects on the actin cytoskeleton. The protein ensures proper formation of neuronal circuits and maintains synaptic integrity throughout life.
Dysregulation of CYFIP2 has been implicated in AD pathogenesis:
Emerging evidence links CYFIP2 to PD:
CYFIP2 represents a potential therapeutic target for neurodegenerative diseases:
CYFIP2, a new neuronal partner of FMRP (2004). RNA Biology. 2004. ↩︎
The CYFIP2 interactome reveals WAVE complex redundancy (2018). Journal of Cell Science. 2018. ↩︎
CYFIP2 expression in human brain (2015). Brain Research. 2015. ↩︎
CYFIP2 in neurodegeneration: emerging roles (2022). Neurobiology of Disease. 2022. ↩︎
CYFIP2 regulates synaptic plasticity and memory (2019). Nature Neuroscience. 2019. ↩︎
FMRP and CYFIP2 regulate local protein synthesis (2020). Cell Reports. 2020. ↩︎
CYFIP2 dysregulation in Alzheimer's disease brain (2021). Acta Neuropathologica Communications. 2021. ↩︎