DWORF

DWorf (DWORF, Dwarf Open Reading Frame) is a small, conserved micropeptide expressed primarily in cardiac and slow-twitch skeletal muscle that modulates calcium handling in the sarcoplasmic reticulum. Initially annotated as part of a putative long noncoding RNA, the locus was later shown to encode a functional peptide that integrates into the sarcoplasmic reticulum membrane.

DWORF interacts with the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and acts indirectly to increase SERCA activity by displacing endogenous inhibitory peptides such as phospholamban and sarcolipin. By relieving SERCA inhibition, DWORF enhances calcium uptake into the sarcoplasmic reticulum, which can accelerate cardiomyocyte relaxation and improve contractile function. These effects have made DWORF of interest in studies of cardiac physiology and heart failure.

Expression of DWORF is regulated developmentally and varies among muscle types; it is conserved in vertebrates, suggesting an evolutionarily preserved role in muscle calcium regulation. Experimental overexpression or gene therapy approaches in animal models have reported improvements in cardiac performance, while reduced DWORF expression has been associated with impaired calcium handling in some disease models. Ongoing research seeks to clarify physiological regulation, detailed structure–function relationships, and therapeutic potential for cardiac disorders.