GULP1 (GULP PTB domain containing engulfment adaptor 1) is a multifunctional adapter protein with primary roles in phagocytosis and cellular trafficking. Mechanistically, GULP1 facilitates the clearance of apoptotic cells by functioning as an engulfment adaptor, with knockdown studies reducing phagocytosis by approximately 40% 1. GULP1 interacts with amyloid precursor protein (APP) to regulate amyloid-β production through modulation of autophagy and APP processing via interaction with autophagy-related protein ATG14 23. Additionally, GULP1 acts as a KEAP1-binding protein that regulates the NRF2-KEAP1 signaling axis, maintaining NRF2 cytoplasmic sequestration 4. Disease relevance spans multiple malignancies and neurodegenerative conditions. GULP1 is significantly overexpressed in hepatocellular carcinoma, independently predicting recurrence and influencing epithelial-mesenchymal transition via ARF6 and β-catenin pathways 5. In pancreatic cancer, GULP1 downregulation inhibits cell proliferation and invasion through HIPPO, mTOR, and RTK pathway regulation 6. In Alzheimer's disease, GULP1 phosphorylation by atypical PKC modulates APP processing and amyloid-β generation 2. GULP1 silencing in urothelial carcinoma confers cisplatin resistance through NRF2 pathway activation 47. Clinically, GULP1 serves as a non-invasive diagnostic and prognostic biomarker with potential as an immunotherapy predictor and therapeutic target across multiple cancer types.