In contrast to the wealth of information available on palmitoylating enzymes, our understanding of the proteins that regulate protein depalmitoylation is poor. Two main candidate thioesterases have been identified. Protein palmitoyl thioesterase 1 (Ppt1) depalmitoylates H-Ras and different G subunits in vitro (Camp and Hofmann, 1993) . Although there are reports that a cytosolic pool of Ppt1 may be present in cells (Kim et al., 2008) , this protein is thought to be predominantly localized to the lysosomal lumen (Hellsten et al., 1996) , where it is believed to function in depalmitoylation reactions occurring during protein degradation. Acyl protein thioesterase 1 (Apt1) reportedly displays thioesterase activity toward G i  1 , H-Ras, eNOS, and certain viral proteins (Duncan and Gilman, 1998; Yeh et al., 1999; Veit and Schmidt, 2001) but is inactive against other proteins such as caveolin (Yeh et al., 1999; Veit and Schmidt, 2001) . Importantly, Apt1 has a cytosolic localization, suggesting that it can regulate cellular palmitoylation dynamics. In support of this idea, overexpression of Apt1 into HEK293 cells was reported to increase the rate of removal of radiolabeled palmitate from G s  in pulse-chase experiments (Duncan and Gilman, 1998) .