ADF/cofilins drive cytoskeletal dynamics by promoting the disassembly of "aged" 
ADP-actin filaments. Mammals express several ADF/cofilin isoforms, but their 
specific biochemical activities and cellular functions have not been studied in 
detail. Here, we demonstrate that the muscle-specific isoform cofilin-2 promotes 
actin filament disassembly in sarcomeres to control the precise length of thin 
filaments in the contractile apparatus. In contrast to other isoforms, cofilin-2 
efficiently binds and disassembles both ADP- and ATP/ADP-Pi-actin filaments. We 
mapped surface-exposed cofilin-2-specific residues required for ATP-actin 
binding and propose that these residues function as an "actin nucleotide-state 
sensor" among ADF/cofilins. The results suggest that cofilin-2 evolved specific 
biochemical and cellular properties that allow it to control actin dynamics in 
sarcomeres, where filament pointed ends may contain a mixture of ADP- and 
ATP/ADP-Pi-actin subunits. Our findings also offer a rationale for why cofilin-2 
mutations in humans lead to myopathies.