Palmitoylation: A new mechanism for control of NCX1 function

[Display omitted] •NCX1 is palmitoylated by zDHHC5 and depalmitoylated by APT1.•Palmitoylation increases NCX1 affinity for lipid rafts and creates a XIP binding site.•XIP binding attenuates NCX1 function leading to increased intracellular calcium.•A deeper understanding of NCX1 palmitoylation is required to control localization and function of ion channels, pumps, and exchangers. A paper by Gök et al., identified Zinc Finger DHHC-Type Palmitoyltransferase 5 (zDHHC5) and Acyl-Protein Transferase 1 (APT1) as the enzymes responsible for the dynamic palmitoylation of NCX1. Palmitoylation occurs at the cell surface and increases the affinity of NCX1 for lipid rafts. Additionally, they discovered that palmitoylation controls the affinity of NCX1 for exchange inhibitory protein (XIP) and regulates intracellular calcium concentration. These findings provide new insights into endogenous control of NCX1 function and will drive future investigations directed at understanding its full potential.