PMVK (phosphomevalonate kinase) catalyzes the ATP-dependent phosphorylation of mevalonate 5-phosphate to mevalonate diphosphate, a critical step in the mevalonate pathway for biosynthesis of cholesterol and polyisoprenoid metabolites 1. Beyond its canonical metabolic role, PMVK exhibits non-canonical functions in cell signaling and immunity. PMVK stabilizes β-catenin signaling through two mechanisms: its product mevalonate 5-diphosphate competitively inhibits CKIα-mediated β-catenin phosphorylation, while PMVK directly phosphorylates β-catenin at Ser184 2. Additionally, PMVK phosphorylates and stabilizes glutamate decarboxylase 1, promoting synthesis of 4-acetaminobutyric acid that suppresses CD8+ T cell activation in the tumor microenvironment 3. Clinically, PMVK mutations cause porokeratosis, an autoinflammatory keratinization disease characterized by aberrant skin lesions 4. Loss-of-function PMVK variants result in defective mevalonate pathway function, and topical cholesterol/lovastatin therapy (replenishing end-products while blocking toxic precursor accumulation) effectively treats PMVK-associated porokeratosis 1. PMVK also promotes cancer progression through β-catenin signaling and DNA repair pathway support; PMVK inhibition enhances radiosensitivity in lung cancer by impairing homologous recombination repair 5, and blocks hepatocellular carcinoma progression when combined with immune checkpoint inhibition 3.