PHOSPHO2 is a haloacid dehalogenase superfamily phosphatase with specialized substrate specificity. Its primary function is dephosphorylation of pyridoxal 5'-phosphate (PLP), exhibiting high catalytic activity (Vmax of 633 nmol min⁻¹ mg⁻¹, Km of 45.5 µM) toward this substrate 1. Unlike the structurally similar PHOSPHO1 phosphatase, PHOSPHO2 shows relatively poor activity toward phosphoethanolamine and phosphocholine, with substrate selectivity determined by subtle charge distribution differences in the active site 1. The enzyme contains three conserved catalytic motifs characteristic of the haloacid dehalogenase superfamily, with key aspartate residues essential for catalytic activity 1. Regarding disease relevance, PHOSPHO2 expression is significantly upregulated in hepatocellular carcinoma (HCC) tissues compared to normal liver, and elevated PHOSPHO2 expression correlates with poor overall survival in HCC patients 2 3. PHOSPHO2 was identified as a key prognostic and diagnostic biomarker for liver cancer 2. Functionally, PHOSPHO2 knockdown reduces HCV antiviral-induced HCC cell proliferation and migration 3, suggesting PHOSPHO2 contributes to hepatocarcinogenesis mechanisms. These findings indicate PHOSPHO2 has potential clinical significance as a therapeutic target and prognostic indicator in HCC.