[1] Roth and colleagues showed that the yeast Akr1p protein could palmitoylate Yck2p in vitro and inferred that the DHHC domain defined a large family of palmitoyltransferases.

[3] However, a recent study questions the involvement of classical enzyme-substrate recognition and specificity in the palmitoylation reaction.

Conserved motifs within protein sequences point towards the most important amino acid residues for function.

It runs on a ping-pong mechanism, where the cysteine attacks the acyl-CoA to form an S-acylated DHHC, and then the acyl group is transferred to the substrate.

Two missense mutations within the DHHC domain of ZDHHC9 were identified in X-linked mental retardation associated with a Marfanoid Habitus.

[12] A gene knockout experiment of the mouse homologue of ZDHHC13 showed hair loss, severe osteoporosis, and systemic amyloidosis, both of AL and AA depositions.