Lethal small molecules are helpful probes to uncover and characterize novel cell dying pathways and biochemical mechanisms. Ideas are convinced that the synthetic oxime-that contains small molecule caspase-independent lethal 56 (CIL56) induces an unconventional type of nonapoptotic cell dying dissimilar to necroptosis, ferroptosis, along with other pathways. CIL56-caused cell dying needs a catalytically active protein S-acyltransferase complex including the enzyme ZDHHC5 as well as an accessory subunit GOLGA7. The ZDHHC5-GOLGA7 complex is mutually stabilizing and localizes towards the plasma membrane. CIL56 inhibits anterograde protein transport in the Golgi apparatus, which can be lethal poor ongoing ZDHHC5-GOLGA7 complex-dependent retrograde protein trafficking in the plasma membrane to internal sites. Other oxime-that contains small molecules, structurally dissimilar to CIL56, may trigger cell dying using it . path. These results define an unconventional type of nonapoptotic cell dying controlled by protein S-acylation.