PXYLP1 (2-phosphoxylose phosphatase 1) is a Golgi-localized phosphatase that catalyzes 2-O-dephosphorylation of xylose residues in the glycosaminoglycan (GAG)-protein linkage region of proteoglycans 1. This enzyme plays a critical regulatory role in GAG biosynthesis by removing phosphate groups from the trisaccharide intermediate (Galβ1-3Galβ1-4Xyl(2-O-phosphate)) during linkage region maturation 1. Dephosphorylation is essential for initiating efficient elongation of heparan sulfate and chondroitin sulfate chains, as polymerization cannot proceed when xylose remains phosphorylated 1. PXYLP1 interacts functionally with glucuronyltransferase-I and coordinates with FAM20B kinase to regulate transient phosphorylation dynamics 1. Knockdown studies demonstrate that PXYLP1 inhibition reduces GAG chain synthesis, confirming its necessity for productive proteoglycan biosynthesis 1. Beyond its primary metabolic role, PXYLP1 has emerged as a prognostic biomarker in epithelial ovarian cancer as part of disease-free survival prediction models 2 and head and neck squamous cell carcinoma prognostic signatures 3. Additionally, PXYLP1 DNA methylation changes in sperm can be inherited by offspring following paternal cannabis exposure, suggesting epigenetic regulatory significance 4.