Cofilin-2

Cofilin-2 (CFL2) is a 166-amino-acid actin-binding protein that reversibly controls actin polymerization and depolymerization in a pH-sensitive manner (UniProt: Q9Y281). It binds G- and F-actin in equimolar ratios and is the major structural component of intranuclear and cytoplasmic actin rods. The protein is essential for muscle maintenance and may regulate sarcomeric actin isoform exchange during postnatal development (UniProt: Q9Y281).

In UniProt, CFL2 is associated with nemaline myopathy 7 (NEM7, MIM 610687), a congenital muscle disorder characterized by weakness and abnormal rod-shaped structures in muscle fibers (UniProt: Q9Y281). The protein's actin-regulatory function suggests roles in cytoskeletal dynamics across tissues.

CFL2 is elevated in Alzheimer's disease: proteomics analysis of post-mortem AD brain tissue versus age-matched controls identified CFL2 as upregulated with a mean log2 fold-change of 0.59 across subcellular fractions (Chaparral AD proteomics). This increase may reflect altered cytoskeletal dynamics or actin-related pathology in AD pathogenesis, though the functional significance requires further investigation.