Pmvk, or phosphomevalonate kinase, is an enzyme that catalyzes the conversion of mevalonate 5-phosphate to mevalonate 5-diphosphate in the mevalonate pathway [5]. This pathway is crucial as it is involved in the synthesis of cholesterol and other isoprenoids, which play vital roles in cell membrane structure, protein prenylation, and the production of signaling molecules.

Mutations in Pmvk have been associated with porokeratosis, a rare chronic progressive hypokeratotic skin disease. For instance, a novel heterozygous missense variant c.207G>T (p.Lys69Asn) in the PMVK gene was identified as the causative variant in a Chinese porokeratosis family [1]. Additionally, linear porokeratosis has been associated with a combination of germline and somatic mutations in Pmvk [4]. In cancer research, depletion of PMVK in hepatocellular carcinoma (HCC) cells facilitates CD8+ T cell activation and suppresses tumor growth. PMVK phosphorylates and stabilizes glutamate decarboxylase 1 (GAD1), increasing the synthesis of γ-aminobutyric acid (GABA), which is then converted to 4-acetaminobutyric acid (4-Ac-GABA) that suppresses CD8+ T cell activation [2]. In lung cancer cells, knockdown of PMVK enhances radiosensitivity through ubiquitination of the replication protein A1, impairing the homologous recombination DNA repair pathway [3].

In conclusion, Pmvk is essential for the mevalonate pathway. Research on Pmvk-related mutations, especially in porokeratosis and cancer, using genetic models such as knockdowns and mutational analyses, has provided insights into the role of Pmvk in disease pathogenesis. These studies may potentially lead to the development of novel therapeutic strategies for treating porokeratosis and enhancing cancer therapies.