LCMT1 (leucine carboxyl methyltransferase 1) is a critical enzyme that methylates the C-terminal leucine residue of protein phosphatase 2A (PP2A) catalytic subunits, regulating PP2A activity and substrate specificity 12. This methylation is essential for proper PP2A holoenzyme assembly and function, controlling the binding of regulatory B subunits that determine substrate targeting 12. LCMT1 functions through an equilibrium with protein phosphatase methylesterase-1 (PME-1), which demethylates PP2A, and this balance is crucial for mitotic spindle size regulation and proper cell division 3. Clinically, LCMT1 has complex roles in cancer: it acts as a tumor suppressor in prostate cancer by targeting androgen receptor signaling 1, but promotes hepatocellular carcinoma proliferation through metabolic reprogramming 4. LCMT1 also regulates glucose homeostasis by controlling hepatic glycogen metabolism 5, and its degradation contributes to tau hyperphosphorylation in Alzheimer's disease during chr16 hypoxia 6. The enzyme protects against oxidative stress through PP2A-mediated dephosphorylation mechanisms 7 and regulates autophagy pathways important for lipid metabolism 8. These diverse functions highlight LCMT1 as a central regulator of cellular homeostasis with significant therapeutic potential.