Previous studies revealed a crucial role of 5-HT1A receptor palmitoylation at its C-terminal cysteine residues Cys417 and Cys420 for 5-HT1A/Gi-protein coupling and effector-mediated signaling.3 An important 5-HT1A receptor palmitoyl acyltransferase is the zinc finger DHHC-type palmitoyltransferase 21 (ZDHHC21) with epigenetic downregulation of ZDHHC21 linked to major depression and suicide.3 Receptor palmitoylation targets it to cholesterol-rich membrane microdomains. Here, HTR1A is linked to major depressive disorder.