Palmitoylation of target proteins, by the palmitoyltransferase ZHHC21, maintains oxidative phosphorylation and is necessary for the viability of AML cells and stem cells. AK2 is palmitoylated by ZHHC21, and AK2 palmitoylation is necessary for its localization to the mitochondria where it regulates oxidative phosphorylation. Chemical or genetic inhibition of ZHHC21 prevents the localization of AK2 to the mitochondria, decreases oxidative phosphorylation, reduces ATP, and inhibits the growth and viability of AML cells. Professional illustration by Patrick Lane, ScEYEnce Studios.