CFL2

CFL2 is the gene symbol for cofilin-2, a member of the actin-depolymerizing factor/cofilin family. Cofilins regulate actin dynamics by severing and depolymerizing filamentous actin (F-actin), enabling turnover and remodeling of the cytoskeleton. Cofilin-2 is the muscle-specific isoform, predominantly expressed in skeletal and cardiac muscle, where it contributes to sarcomere organization and muscle fiber maintenance. It localizes to actin-rich structures in muscle cells, such as Z-lines and associated regions.

Regulation of CFL2 activity occurs primarily through phosphorylation. Serine-3 phosphorylation by LIM kinases (LIMK1/2) inhibits actin severing, while dephosphorylation by phosphatases such as SSH1 reactivates it. This regulatory cycle is integrated with broader signaling pathways that control cytoskeletal dynamics, including those mediated by Rho family GTPases and ROCK.

Genetics and evolution: CFL2 is one of two vertebrate cofilin genes, the other being CFL1, and is conserved across vertebrates. The CFL2 gene encodes the muscle-specific cofilin-2 protein, with orthologs identified in a wide range of species, reflecting its fundamental role in actin regulation within muscle tissue.

Clinical relevance: Research has investigated the role of CFL2 in muscle biology and disease, including studies on how variants or dysregulated activity may affect muscle fiber integrity and cardiac muscle function. The contribution of CFL2 to human disease remains an area of active investigation, with evidence primarily from model systems and exploratory human studies.