Endoplasmic reticulum palmitoyl acyltransferase that mediates palmitoylation of proteins such as AMFR, CALX, ITPR1 and TFRC (PubMed:22314232, PubMed:22728137, PubMed:25368151, PubMed:28826475). Palmitoylates calnexin (CALX), which is required for its association with the ribosome-translocon complex and efficient folding of glycosylated proteins (PubMed:22314232). Mediates palmitoylation of AMFR, promoting AMFR distribution to the peripheral endoplasmic reticulum (PubMed:22728137). Together with SELENOK, palmitoylates ITPR1 in immune cells, leading to regulate ITPR1 stability and function (PubMed:25368151). Stearoyltransferase that mediates stearoylation of TFRC to inhibit TFRC-mediated activation of the JNK pathway and mitochondrial fragmentation (PubMed:26214738). hexadecanoyl-CoA + L-cysteinyl-[protein] = CoA + S-hexadecanoyl-L-cysteinyl-[protein] L-cysteinyl-[protein] + octadecanoyl-CoA = CoA + S-octadecanoyl-L-cysteinyl-[protein] Homooligomerizes (PubMed:28826475). Interacts with SELENOK (PubMed:25368151). When not palmitoylated, accumulates to dot-like structures in the endoplasmic reticulum (PubMed:28826475). The DHHC domain is required for palmitoyltransferase activity. The C-terminal di-lysine motif confers endoplasmic reticulum localization. Palmitoylated at 3 different sites by ZDHHC16 (PubMed:28826475). The combination of the different palmitoylation events strongly affects the quaternary assembly of ZDHHC6, its localization, stability and function (PubMed:28826475). Palmitoylation at Cys-328 accelerates the turnover of ZDHHC6 (PubMed:28826475). Depalmitoylated by LYPLA2 (PubMed:28826475). Belongs to the DHHC palmitoyltransferase family.