PSPH (phosphoserine phosphatase) catalyzes the final irreversible step in L-serine biosynthesis from carbohydrates, converting O-phospho-L-serine to L-serine 1. This enzyme functions as a homodimer in the cytosol and plays a central role in metabolic homeostasis by controlling serine availability for protein synthesis, amino acid production, nucleotide metabolism, and glutathione synthesis 1. L-serine can also be racemized to D-serine, which acts as a neuromodulator at N-methyl-D-aspartate receptors 2. PSPH expression is epigenetically regulated through histone acetylation and m6A modification in cancer cells 34. The enzyme is significantly upregulated in multiple malignancies including hepatocellular carcinoma, glioblastoma, and bladder cancer, where elevated PSPH promotes metabolic reprogramming to support tumor growth and therapeutic resistance 156. PSPH amplifications occur in approximately 13% of glioblastomas and correlate with poor prognosis and immunosuppression 5. In skeletal muscle, PSPH contributes to metabolic rewiring during hypertrophy by channeling glycolytic intermediates into anabolic pathways 7. Clinically, PSPH inhibition shows therapeutic potential in temporal lobe epilepsy by reducing D-serine levels and seizure activity 2, and combined targeting of PSPH with other agents demonstrates efficacy in cancer models 5.