ICMT (isoprenylcysteine carboxyl methyltransferase) catalyzes the post-translational methylation of isoprenylated C-terminal cysteine residues, representing the final enzymatic step in the prenylation pathway 1. This modification is essential for proper membrane localization of CAAX motif-containing proteins, particularly oncoproteins like Ras, and CXC-class Rab proteins 1. ICMT activity is critical for normal development, as ICMT-deficient embryos are embryonic lethal, though conditional tissue-specific inactivation shows no obvious pathology 1. ICMT promotes cancer progression through multiple mechanisms. ICMT overexpression enhances lung metastasis in vivo and promotes cellular invasion and migration through enhanced invadopodia formation 2. In hepatocellular carcinoma, ICMT is overexpressed in ~70% of tumors and drives growth, survival, migration, and chemoresistance via Ras/Raf/Mek/Erk signaling and epithelial-mesenchymal transition 3. ICMT inhibition shows promise as an anti-cancer strategy, with selective ICMT inhibitors blocking Ras-induced oncogenic transformation 14. Beyond cancer, ICMT inhibitors delay cellular senescence in Hutchinson-Gilford progeria syndrome by blocking progerin methylation and improve survival in disease models 5. These findings establish ICMT as a therapeutic target across multiple pathologies.