Huntingtin interacting protein 14 (HIP14), a membrane-bound palmitoyl transferase, palmitoylates a number of neuronal proteins (including Huntingtin) and affects the trafficking, stability, aggregation, and/or functional activity of substrate proteins. HIP14 contains an N-terminal ankyrin repeat domain that may function in its substrate recognition. Sequence analysis suggests that the HIP14 ankyrin repeats share approximately 50% identity with the ankyrin repeats of G9a and G9a-like protein (GLP) histone lysine methyltransferases. The crystal structure of the HIP14 ankyrin repeats reveals a surface aromatic cage, formed by two tryptophans, one tyrosine, and one methionine. The all-hydrophobic cage resembles the tri-methylated lysine binding pocket of the plant homeodomain (PHD) of human BPTF (bromodomain and PHD domain transcription factor).