PUDP (pseudouridine 5'-phosphatase), encoded by the HDHD1 gene located on chromosome X, functions as a highly specific phosphatase that dephosphorylates pseudouridine 5'-phosphate, a potential intermediate in RNA degradation 1. The enzyme exhibits exceptional substrate specificity with a Km of 0.3 μM for pseudouridine 5'-phosphate and catalytic efficiency at least 1000-fold higher than for other phosphate esters, including 5'-UMP 1. PUDP belongs to the haloacid dehalogenase family of phosphatases, requires Mg2+ for activity, and is inhibited by Ca2+ and vanadate 1. The enzyme facilitates the excretion of pseudouridine intact in urine, as pseudouridine is not metabolized in mammals 1. PUDP demonstrates sex-linked expression patterns, with 1.5-fold higher activity in female erythrocytes compared to males, consistent with partial X-inactivation escape 1. The gene is frequently deleted in X-linked ichthyosis patients alongside the STS gene, resulting in negligible enzyme activity (<10% of controls) 1. PUDP is among 14 X-chrX genes showing consistent expression patterns across tissues in sex chromosome X, suggesting potential roles in epigenetic regulation 2.