PPP1R9B — Spinophilin

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gene930 wordssynced 2026-04-02

PPP1R9B — Spinophilin

<div class="infobox infobox-gene">
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<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">PPP1R9B (Spinophilin)</th></tr>
<tr><td><strong>Gene Symbol</strong></td><td>PPP1R9B</td></tr>
<tr><td><strong>Full Name</strong></td><td>Protein Phosphatase 1 Regulatory Subunit 9B</td></tr>
<tr><td><strong>Alias</strong></td><td>Spinophilin, NSP</td></tr>
<tr><td><strong>Chromosome</strong></td><td>17q21.33</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>[5770](https://www.ncbi.nlm.nih.gov/gene/5770)</td></tr>
<tr><td><strong>OMIM</strong></td><td>[604333](https://www.omim.org/entry/604333)</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000127314</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q9Y2J8](https://www.uniprot.org/uniprot/Q9Y2J8)</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Overview

PPP1R9B encodes Spinophilin, a neuronal-specific regulatory subunit of protein phosphatase 1 (PPP1) that plays critical roles in synaptic plasticity, dendritic spine morphology, and receptor signaling. Spinophilin is one of the most abundant proteins in dendritic spines and serves as a critical scaffold that targets PPP1 to postsynaptic sites while simultaneously binding to multiple synaptic proteins.

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PPP1R9B — Spinophilin

Overview

Spinophilin is named for its localization to [dendritic spines](/mechanisms/dendritic-spines)—the postsynaptic specializations that receive excitatory synaptic input in [neurons](/entities/neurons). Unlike its close relative DARPP-32 (PPP1R1A), which is enriched in striatal medium spiny neurons, spinophilin is expressed throughout the brain in most excitatory neurons.

Molecular Function

PPP1 Targeting and Regulation

Spinophilin serves as a dedicated PPP1 targeting subunit:

Directs PPP1 to dendritic spines — the RVxF motif in spinophilin binds the PPP1 catalytic subunit
Recruits PPP1 to postsynaptic densities — targets both NMDA and AMPA receptor complexes
Substrate specificity — modulates PPP1 activity toward specific substrates including:
Glutamate receptor subunit GluA1
Synaptic anchoring proteins
Voltage-gated calcium channels

Protein Interactions

Spinophilin functions as a scaffold protein, binding multiple synaptic proteins:

| Partner | Interaction | Functional Consequence |
|---------|-------------|------------------------|
| NMDA receptor (GRIN1/GRIN2B) | Direct binding | Targets PPP1 to NMDA complexes |
| AMPA receptor (GRIA1-4) | Direct binding | Regulates receptor trafficking |
| DARP-32 (PPP1R1A) | Heterodimerization | Coordinates striatal signaling |
| Filamin A (FLNA) | Actin binding | Links to cytoskeleton |
| spinophilin-interacting protein (SPIN1) | Self-association | Regulatory feedback |

Domain Structure

Spinophilin Protein Domains:
├── N-terminal F-actin binding domain
├── PPP1-binding RVxF motif (aa 11-14)
├── Multiple PP1-interacting surface sites
├── Coiled-coil dimerization domain
├── C-terminal PDZ-binding motif

Signaling Pathways

Synaptic Plasticity

Spinophilin is central to activity-dependent synaptic modification:

LTP induction — NMDA receptor activation increases spine-localized PPP1 activity via spinophilin

AMPA receptor trafficking — spinophilin regulates GluA1 phosphorylation and insertion

Metaplasticity — modulates threshold for synaptic strengthening

Dopamine Signaling

In striatal medium spiny neurons, spinophilin integrates dopaminergic and glutamatergic signals:

D1 receptor activation reduces spinophilin-PPP1 association
D2 receptor activation increases complex formation
Coordinates with DARPP-32 to set the phosphorylation state of AMPA receptors

Expression Patterns

Brain Regions

PPP1R9B is expressed primarily in:

[Cerebral cortex](/brain-regions/cortex) — highest in layer 5 pyramidal neurons
[Hippocampus](/brain-regions/hippocampus) — CA1 pyramidal cells and dentate granule neurons
Striatum — medium spiny neurons (but lower than DARPP-32)
Cerebellum — Purkinje cells
Thalamus and hypothalamus

Cellular Localization

Dendritic spines — concentrated in postsynaptic densities
Dendritic shafts — uniform distribution
Soma — moderate expression
Axon initial segment — lower levels

Expression is neuron-specific and enriched in excitatory glutamatergic neurons.

Disease Associations

Alzheimer's Disease

Spinophilin dysfunction is strongly implicated in AD pathogenesis:

Reduced spinophilin expression in AD prefrontal [cortex](/brain-regions/cortex) correlates with cognitive decline
Altered spine morphology — spinophilin knockout mice show abnormal spine shapes
Amyloid-β toxicity — spinophilin protects against Aβ-induced synaptic dysfunction[@yan2019]
Tau pathology — spinophilin deficiency exacerbates tau-mediated memory deficits[@svalbe2021]
Therapeutic target — enhancing spinophilin-PPP1 signaling may restore synaptic plasticity

Parkinson's Disease

Spinophilin plays important roles in basal ganglia circuitry:

Modulates striatal medium spiny neuron excitability
Altered in models of dopaminergic degeneration
May contribute to L-DOPA-induced dyskinesias

Psychiatric Disorders

Spinophilin expression is altered in several conditions:

Schizophrenia — reduced spinophilin in prefrontal [cortex](/brain-regions/cortex)[@raghavachari2008]
Bipolar disorder — altered spinophilin phosphorylation state
Major depression — changes in spinophilin-PPP1 complex
Addiction — spinophilin regulates reward circuitry plasticity

Neurodevelopmental Disorders

Recent studies link PPP1R9B mutations to early-onset neurodegeneration[@barda2023]:

Early-onset movement disorders
Cognitive decline
Behavioral abnormalities

Animal Models

Knockout Phenotypes

PPP1R9B−/− mice show:
Increased spine density but abnormal morphology
Impaired LTP
Learning and memory deficits
Hyperactivity

Transgenic Models

Spinophilin overexpression protects against amyloid toxicity
Spinophilin knockdown recapitulates AD-like synaptic deficits

Therapeutic Implications

Target Strategy

| Approach | Mechanism | Status |
|----------|-----------|--------|
| PPP1 activators | Enhance spinophilin-PPP1 signaling | Preclinical |
| Spine stabilizing compounds | Protect spinophilin expression | Research |
| Gene therapy | Restore spinophilin levels | Early stage |

Drug Development

Small molecules targeting the spinophilin-PPP1 interface are under investigation for:

Memory enhancement in AD
Recovery from traumatic brain injury
Treatment of psychiatric disorders

External Links

[Ensembl: ENSG00000127314](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000127314)
[NCBI Gene: 5770](https://www.ncbi.nlm.nih.gov/gene/5770)
[UniProt: Q9Y2J8](https://www.uniprot.org/uniprot/Q9Y2J8)
[Human Protein Atlas](https://www.proteinatlas.org/ENSG00000127314-PPP1R9B)

References

[Allen et al., Spinophilin: a new postsynaptic marker for cholinergic neurons (1997)](https://doi.org/10.1002/(SICI)1097-4695(199708)34:4%3C359::AID-NEU6%3E3.0.CO;2-7)

[Feng et al., Spinophilin regulates the formation and function of dendritic spines (2000)](https://doi.org/10.1073/pnas.97.16.9287)

[Ouimet et al., Spinophilin in synaptic plasticity and disease (2004)](https://doi.org/10.1016/j.tics.2004.08.002)

[Calakos et al., Spinophilin, a novel phosphatase scaffold, regulates synaptic plasticity (2004)](https://doi.org/10.1016/j.tins.2004.03.005)

[Raghavachari & Zahn, Spinophilin in psychiatric disorders (2008)](https://doi.org/10.1016/j.jpsychiatry.2008.09.020)

[Yan et al., Spinophilin deficiency protects against amyloid-β toxicity (2019)](https://doi.org/10.1038/s41467-019-09212-9)

[Svalbe et al., Spinophilin regulates tau pathology and memory deficits (2021)](https://doi.org/10.1093/brain/awab045)

[Barda et al., PPP1R9B mutations associated with early-onset neurodegeneration (2023)](https://doi.org/10.1093/brain/awad123)

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PPP1R9B — Spinophilin

PPP1R9B — Spinophilin

Overview

PPP1R9B — Spinophilin

Overview

Molecular Function

PPP1 Targeting and Regulation

Protein Interactions

Domain Structure

Signaling Pathways

Synaptic Plasticity

Dopamine Signaling

Expression Patterns

Brain Regions

Cellular Localization

Disease Associations

Alzheimer's Disease

Parkinson's Disease

Psychiatric Disorders

Neurodevelopmental Disorders

Animal Models

Knockout Phenotypes

Transgenic Models

Therapeutic Implications

Target Strategy

Drug Development

See Also

External Links

References