PSAT1 catalyzes the second step of L-serine biosynthesis, converting 3-phosphohydroxypyruvate and L-glutamate to O-phosphoserine and α-ketoglutarate in a pyridoxal 5'-phosphate-dependent reaction. Beyond canonical serine synthesis, PSAT1 serves a noncanonical ferroptosis-suppressive function: following phosphorylation by CAMK2A in response to interferon-γ, PSAT1 stabilizes GPX4 by promoting its hydroxylation via α-ketoglutarate-dependent PHD3 activity, thereby inhibiting autophagy-mediated degradation. In cancer contexts, PSAT1 is frequently upregulated through multiple regulatory mechanisms. HIF-1α activation enhances PSAT1 expression under serine/glycine deprivation in glioblastoma, promoting glucose-derived serine biosynthesis and cell proliferation 1. In colorectal cancer, AURKB suppresses HNRNPM-mediated PSAT1 mRNA degradation, elevating PSAT1 protein levels and driving tumor progression 2. NRF2-dependent transcriptional upregulation of PSAT1 occurs in non-small cell lung cancer and correlates with poor prognosis 3. Epigenetic regulation via histone acetylation controls PSAT1 expression in hepatocellular carcinoma 4, and m6A modification stabilizes PSAT1 mRNA in sorafenib-resistant HCC 5. Clinically, PSAT1 inhibition enhances immunotherapy sensitivity in triple-negative breast cancer by restoring ferroptosis 6. Blocking PSAT1 synergizes with GLS inhibitors to overcome glutamine-addiction plasticity in breast cancer 7, and serine/glycine dietary restriction synergizes with Psat1-KO to suppress liver tumor formation 8.