NSG1 (neuronal vesicle trafficking associated 1) is a 21 kDa endosomal protein that regulates vesicle trafficking and cellular signaling in neurons and other cell types 1. The protein plays a critical role in maintaining neurite thickness through interaction with the phosphatidylinositol (3,5)-bisphosphate [PtdIns(3,5)P2] machinery, localizing to early endosomes and requiring proper PtdIns(3,5)P2 signaling for correct subcellular distribution 1. NSG1 also regulates sortilin ectodomain shedding through transmembrane domain interactions, modulating ADAM10-mediated proteolytic processing 2. Beyond its neuronal functions, NSG1 demonstrates pathological roles in cancer progression. In esophageal squamous cell carcinoma (ESCC), NSG1 is overexpressed and promotes epithelial-mesenchymal transition through ERK signaling pathway activation 3. Similarly, NSG1 enhances hypopharyngeal squamous cell carcinoma progression via ERK pathway regulation and can be targeted by miR-107 4. NSG1 expression is also elevated in ovarian cancer and serves as a prognostic biomarker 5. Additionally, NSG1 has been identified as a potential diagnostic marker for heart failure and coronary heart disease, though its specific mechanisms in cardiovascular pathology remain unclear 67.