PLPPR1 (phospholipid phosphatase related 1), also known as PRG3, is a phospholipid-metabolizing enzyme with critical roles in nervous system development and cancer biology. Primary Function: PLPPR1 mediates lipid phosphate phosphatase activity and promotes neurite outgrowth in neurons 1. It shows dynamic expression during brain development, with strongest expression in hippocampus and cerebellum, and is localized to neurite extensions 1. Mechanism: Unlike other plasticity-related genes, PLPPR1 executes its neuronal functions through non-enzymatic mechanisms independent of phospholipid degradation 1. In pathological contexts, PLPPR1 interacts with RasGEF1 and undergoes Ras-induced signaling 2. Disease Relevance: PLPPR1 dysregulation is implicated in malignant gliomas, where imbalanced expression levels foster Ras-driven oncogenic amplification, increased proliferation, and cell migration 2. Additionally, PLPPR1 appears in genome-wide association studies of breast cancer, where it metabolizes phospholipids controlling endocytosis and exosome packaging involved in metastasis 3. Clinical Significance: PLPPR1 silencing confers resistance to Ras inhibitors in gliomas, suggesting its potential as a therapeutic target 2.