<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">FLNC Protein</th>
</tr>
<tr>
<td class="label">Gene Name</td>
<td>FLNC</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q14315</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~291 kDa (single chain)</td>
</tr>
<tr>
<td class="label">Family</td>
<td>Filamin family</td>
</tr>
<tr>
<td class="label">Structure</td>
<td>24 Ig-like repeats + 2 hinge regions</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Skeletal muscle, heart, brain, endothelium</td>
</tr>
<tr>
<td class="label">Tissue Specificity</td>
<td>Highest in muscle, moderate in brain</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/myofibrillar-myopathy" style="color:#ef9a9a">Myofibrillar Myopathy</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">22 edges</a></td>
</tr>
</table>
<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">FLNC Protein</th>
</tr>
<tr>
<td class="label">Gene Name</td>
<td>FLNC</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q14315</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~291 kDa (single chain)</td>
</tr>
<tr>
<td class="label">Family</td>
<td>Filamin family</td>
</tr>
<tr>
<td class="label">Structure</td>
<td>24 Ig-like repeats + 2 hinge regions</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Skeletal muscle, heart, brain, endothelium</td>
</tr>
<tr>
<td class="label">Tissue Specificity</td>
<td>Highest in muscle, moderate in brain</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/myofibrillar-myopathy" style="color:#ef9a9a">Myofibrillar Myopathy</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">22 edges</a></td>
</tr>
</table>
Filamin C (FLNC), also known as filamin-2 or ABP-L (actin-binding protein L), is a large actin-crosslinking protein that plays essential roles in cytoskeletal organization, cell signaling, and mechanical stability. As a member of the filamin family (which also includes FLNA/filamin A and FLNB/filamin B), FLNC is characterized by its unique ability to form flexible networks through repeated actin-binding domains and flexible hinge regions. FLNC is predominantly expressed in skeletal and cardiac muscle, where it localizes to Z-discs and the myotendinous junction, but is also expressed in non-muscle tissues including the brain[@van2001].
In [neurons](/entities/neurons) and other cell types, FLNC contributes to cytoskeletal organization, membrane receptor signaling, and cell migration. Mutations in FLNC are associated with myofibrillar myopathies and cardiomyopathies, highlighting its essential role in muscle integrity. In the central nervous system, FLNC is expressed in neurons where it participates in synaptic function and cytoskeletal dynamics. Its role in neurodegenerative diseases is an emerging area of research[@feng2004].
FLNC possesses an exceptionally large and modular architecture optimized for flexible crosslinking:
N-terminal Actin-Binding Domain (ABD):
FLNC contains two hinge regions:
Hinge 1 (between Ig15-Ig16):
The filamin structure enables:
FLNC organizes the actin cytoskeleton through:
Actin crosslinking: FLNC crosslinks actin filaments into orthogonal and parallel networks, providing mechanical strength and enabling cell shape maintenance[@shepts1999].
Membrane anchorage: Links actin cytoskeleton to membrane proteins and cell adhesion molecules.
Mechanical signaling: Acts as a mechanosensor, transmitting mechanical forces to signaling pathways.
In skeletal and cardiac muscle:
Z-disc integration: FLNC is a major component of Z-discs, where it links actin thin filaments to the membrane and coordinates sarcomere assembly.
Myotendinous junction: Concentrated at the muscle-tendon interface, where it connects the cytoskeleton to extracellular matrix proteins.
Mechanical stability: Provides structural integrity during muscle contraction and relaxation.
In neurons, FLNC has emerging roles:
Synaptic organization: Associates with postsynaptic densities and may contribute to synaptic protein organization.
Axonal cytoskeleton: Contributes to axonal stability and may participate in transport processes.
Cell adhesion: Links membrane proteins to the neuronal cytoskeleton.
FLNC serves as a signaling platform:
Emerging evidence links FLNC to AD pathogenesis:
Cytoskeletal integrity: FLNC contributes to neuronal cytoskeletal stability, and dysfunction may accelerate [tau](/proteins/tau) pathology and synaptic loss.
Synaptic function: As a component of postsynaptic densities, FLNC may be affected by early synaptic alterations in AD.
Protein aggregation: FLNC may co-localize with protein aggregates in disease states, though this is less characterized than for other cytoskeletal proteins.
FLNC may contribute to PD through:
Dopaminergic neuron function: The unique stress on dopaminergic neurons may involve cytoskeletal components like FLNC.
[Alpha-synuclein](/proteins/alpha-synuclein) interactions: Possible interactions between alpha-synuclein and cytoskeletal proteins.
Axonal transport: FLNC's role in transport processes may be relevant to the axonal pathology in PD.
FLNC involvement in ALS includes:
Motor neuron vulnerability: The extremely long axons of motor neurons require robust cytoskeletal support, in which FLNC participates.
Cytoskeletal defects: ALS is associated with cytoskeletal abnormalities, and FLNC may contribute to or be affected by these changes.
Protein aggregation: FLNC may be incorporated into ALS-related aggregates in some cases.
Mutations in FLNC cause myofibrillar myopathy:
Targeting FLNC therapeutically:
FLNC as a biomarker:
Filamin C is a large actin-crosslinking protein essential for cytoskeletal organization in muscle and non-muscle cells. Its modular structure with 24 immunoglobulin-like repeats and flexible hinge regions enables flexible crosslinking of actin filaments into networks that provide mechanical stability and serve as signaling platforms. In muscle cells, FLNC is critical for Z-disc integrity and the myotendinous junction, while in neurons it participates in synaptic organization and axonal cytoskeleton maintenance. Mutations in FLNC cause myofibrillar myopathy and cardiomyopathies, while its role in neurodegenerative diseases is an emerging area of research. Understanding FLNC function may lead to therapeutic strategies for both muscle and neuronal pathologies.