PLBD1 (phospholipase B domain containing 1) is a lysosomal enzyme with aminopeptidase activity that preferentially cleaves hydrophobic amino acids, particularly leucine residues, playing a key role in degrading hydrophobic transmembrane domains within lysosomes. Beyond its canonical proteolytic function, PLBD1 demonstrates broader clinical relevance across multiple disease contexts. In oncology, PLBD1 is highly expressed in multiple cancer types and serves as an independent prognostic factor in gliomas 1. PLBD1 knockdown significantly inhibits glioma cell proliferation and invasion, and the protein associates with immune cell infiltration and checkpoint expression, positioning it as a potential immunotherapeutic target 1. In cardiovascular disease, peripheral blood PLBD1 RNA levels on admission with acute myocardial infarction independently predict left ventricular dysfunction, with odds ratios of 1.43 in external validation cohorts 2. Notably, PLBD1 expression correlates with neutrophil infiltration in ischemic myocardium independent of infarct size 2. In cerebrovascular disease, PLBD1 downregulation follows hypoperfusion-induced cerebral infarction and mediates therapeutic effects through a "shear stress-PLBD1-glycolysis-angiogenesis" axis, enhancing endothelial mechanotransduction and collateral vessel formation 3. Additionally, PLBD1 shows negative correlation with lung adenocarcinoma risk and demonstrates diagnostic utility 4, while PLBD1-AS1 (antisense RNA) shows elevated expression in breast cancer and hepatocellular carcinoma 5, 6. PLBD1 also associates with oxidative stress dynamics in sepsis-related macrophages 7.