AbstractDecapping is a critical step in the control of mRNA stability and the regulation of gene expression. Two major decapping enzymes involved in mRNA turnover have been identified, each functioning in one of the two exonucleolytic mRNA decay pathways in eukaryotic cells. The Dcp2 protein cleaves capped mRNA and initiates 5′ to 3′ degradation; the scavenger decapping enzyme, DcpS, hydrolyzes the cap structure generated by the 3′ to 5′ decay pathway. Consistent with the important role of decapping in gene expression, cap hydrolysis is exquisitely controlled by multiple regulators that influence association with the cap and the catalytic step. In this review, we will discuss the functions of the two different decapping enzymes, their regulation by cis‐elements and trans‐factors, and the potential role of the decapping enzymes in human neurological disorders. Copyright © 2010 John Wiley & Sons, Ltd.This article is categorized under: RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms RNA Turnover and Surveillance > Regulation of RNA Stability