Filamin-A

Filamin-A (FLNA) is a large cytoplasmic scaffolding protein that promotes branching of actin filaments and anchors transmembrane proteins to the actin cytoskeleton, thereby organizing cellular architecture and signaling. It plays critical roles in neuronal migration, ciliogenesis, growth cone guidance, and the formation of cell–cell contacts during vascular and brain development (UniProt: P21333). FLNA is associated with multiple X-linked genetic disorders including periventricular nodular heterotopia, otopalatodigital syndromes, and FG syndrome, reflecting its essential function in cytoskeletal regulation and cellular morphogenesis.

In Alzheimer's disease, Filamin-A is upregulated in post-mortem brain tissue compared to age-matched controls (Chaparral AD proteomics). Quantitative proteomics across four subcellular fractions (P2, P3, S2, S3) showed a mean log2 fold-change of 0.83, indicating consistent elevation of the protein. This upregulation may reflect compensatory cytoskeletal remodeling or synaptic dysfunction associated with neurodegeneration in the AD brain.