USO1 (USO1 vesicle transport factor) is a critical membrane tethering protein that facilitates vesicular transport between the endoplasmic reticulum and Golgi apparatus. The protein functions as a general vesicular transport factor required for intercisternal transport in the Golgi stack and transcytotic fusion processes 1. USO1 exists as a monomeric protein with an N-terminal globular head domain that adopts alternative conformations, potentially regulating precise vesicle docking to Golgi membranes through interaction with Ypt1 GTPase 1. The protein plays essential roles in maintaining proper ER-Golgi network organization, with different isoforms (USO1-N and USO1-T) showing distinct functional properties in liver cancer progression 2. USO1 has significant disease relevance, being overexpressed in multiple cancer types including colon cancer 3, multiple myeloma 4, hepatocellular carcinoma 2, and B-cell acute lymphoblastic leukemia 5. In cancer contexts, USO1 promotes tumor progression by activating ERK signaling pathways and enhancing cell proliferation, migration, and survival 4 3. The protein represents a promising therapeutic target, as its knockdown inhibits cancer cell growth and induces apoptosis across multiple malignancies 5 6.