Post-translation lipid modification has been shown to alter the trafficking, targeting and function of a wide range of membrane proteins. Palmitoylation, one type of lipid modification, involves the thioester linkage of palmitate molecules to specific cysteine residues. Palmitoylation is undertaken by a group of 23 palmitoyl-acyl-tranferase (PAT) enzymes which contain a ZDHHC (zinc-finger and aspartate-histidine-histidine-cysteine) motif(1). The potential role of PAT enzymes in physiological control mechanisms, in the causation of disease and as therapeutic targets is the focus of considerable research (2,3,4). This study uses a bioinformatics approach to screen the genomic and proteomic data available for human PATs in order to identify and prioritise isoforms for future laboratory and clinical investigation. Genomic and proteomic information from the National Centre for Biotechnology Information (NCBI), GeneCards and Uniprot databases was collated and analysed to identify: (a) the number of non-synonymous single-nucleotide polymorphisms (nsSNPs) in PAT genes; (b) their location; and (c) PAT splice variants. The potential of nsSNP to produce damage was analysed using the pre-formulated prediction software systems SNAP, SIFT, Panther, PolyPhen and MutPred as well as damage-prediction scoring system that assigns a damaging score based upon the nature of resulting amino acid (AA) substitutions and their location on functionally important motifs on proteins. An initial screen identified 21,291 nsSNPs, with ~1% displaying high scores (> 50% threshold or equivalent) on the damage-prediction scoring system. Further analysis lead to the prioritisation of six nsSNP candidates; rs111416789 (zDHHC8), rs137852214 (zDHHC9), rs138835172, rs11552044, rs149584176 and rs147199543 (zDHHC24). These nsSNPs are of particular interest due to the nature of the resulting AA substitutions, the close proximity of the substitutions to the enzyme active site and areas involved in post-translational modification, such as palmitoylation and phosphorylation sites. Prioritised nsSNPs will be examined to determine the functional impact of the resulting amino acid changes in the PAT proteins in laboratory based expression systems and assays; those found to alter PAT function will be investigated with respect to their distribution and incidence within appropriate populations and disease groups.