PDXP (pyridoxal phosphatase) is a haloacid dehalogenase (HAD)-family phosphatase with dual enzymatic functions in vitamin B6 metabolism and cytoskeletal regulation 1. As a pyridoxal phosphate (PLP) phosphatase, PDXP catalyzes dephosphorylation of PLP, pyridoxine 5'-phosphate (PNP), and pyridoxamine 5'-phosphate (PMP), with substrate preference order PLP > PNP > PMP, thereby controlling bioactive vitamin B6 levels 2. Additionally, PDXP functions as a serine phosphatase that specifically dephosphorylates Ser-3 in actin-depolymerizing factor/cofilin family proteins like CFL1 and DSTN, regulating cofilin-dependent actin cytoskeleton reorganization required for mitosis and cytokinesis 3. Vitamin B6 deficiency links to cognitive impairment, and PDXP activity inversely correlates with age-dependent PLP decline in the hippocampus, establishing PDXP as a druggable therapeutic target 4. Disease relevance includes acute myeloid leukemia (AML), where elevated PDXP expression promotes cell proliferation through the PI3K/AKT/mTOR pathway 5, and endothelial barrier dysfunction, where PDXP downregulation protects against LPS-induced hyper-permeability 3. The discovery of 7,8-dihydroxyflavone as a PDXP inhibitor provides a pharmacological tool for investigating B6-associated neurological pathologies 4.