QPCT (glutaminyl-peptide cyclotransferase) is a zinc-binding enzyme that catalyzes the cyclization of N-terminal glutamine or glutamate residues to pyroglutamate (pGlu), a critical post-translational modification 1. This enzymatic activity occurs on diverse protein substrates and is particularly important for modifying immune checkpoint proteins like CD47, where QPCT-mediated pyroglutamylation regulates CD47's interaction with signal-regulatory protein alpha (SIRPα) and modulates macrophage-mediated cell clearance 2. QPCT's dysregulation is implicated in multiple pathological contexts. In cancer biology, elevated QPCT expression correlates with poor prognosis in papillary thyroid carcinoma and breast cancer, where it promotes chemotherapy resistance through the MTDH/NF-κB (p65)/QPCT signaling axis 34. QPCT also serves as a biomarker in severe acute pancreatitis and idiopathic normal-pressure hydrocephalus, with elevated CSF levels predicting poor shunt outcomes 56. Additionally, hepatitis B virus upregulates QPCT expression, which reciprocally promotes HBV replication 7. These diverse disease associations underscore QPCT's emerging therapeutic relevance 8, though clinical application remains early-stage.