Acyl-protein thioesterases are enzymes that cleave off lipid modifications on proteins, located on the sulfur atom of cysteine residues linked via a thioester bond.

Acyl-protein thioesterases feature 3 major structural components that determine protein function and substrate processing: 1.

A lid-loop that covers the catalytic site, is highly flexible and is a main factor determining the enzyme's product release rate.

[14] The involvement in controlling the localization of the oncogene Ras has made acyl-protein thioesterases potential cancer drug targets.

Inhibitors for acyl-protein thioesterases have been specifically targeting the hydrophobic substrate tunnel,[16][13] the catalytic site serine[17] or both.