S-Palmitoylation is a post-translational modification consisting in the reversible attachment of palmitate. Little is known about the mechanisms that underlie the dynamics of the process. Using computational modelling we investigated the palmitoylation- depalmitoylation cycles of the ER chaperone calnexin, which requires palmitoylation on 2 sites to be functional. Model based analysis revealed that palmitoylation seems to be an inefficient process where 75% of synthesized calnexin is degraded before it reaches the palmitoylated state. The model also shows that by tuning palmitoyltransferase activity, cells can regulate the abundance of calnexin. This raises the possibility that this apparent inefficiency is a design principle: palmitoylation is timed by a regulatory system that determines cellular calnexin content at the post-transcriptional level.