TMED5 is a transmembrane p24 trafficking protein involved in vesicular protein transport within the early secretory pathway 1. It functions in maintaining Golgi apparatus structure and facilitating protein exchange between Golgi stacks, while remaining non-essential for COPI-mediated retrograde transport. TMED5 interacts with WNT7B to activate canonical Wnt/β-catenin signaling 2, and promotes nuclear autophagy in cellular stress responses. Dysregulation of TMED5 has significant disease relevance across multiple cancer types. In hepatocellular carcinoma, elevated TMED5 expression correlates with worse overall survival and associates with progression 1. TMED5 knockdown suppresses proliferation, migration, and invasion while enhancing apoptosis 1. In cervical cancer, TMED5 upregulation drives malignant phenotypes through multiple regulatory networks, including miRNA-mediated control 23. Similarly, in ovarian cancer, TMED5 activation via the SNHG4/miR-98-5p axis promotes the Wnt/β-catenin pathway 4. TMED5 is also amplified and overexpressed in bladder cancer 5. Clinically, TMED5 accumulation in lysosomes associates with APOE4-induced lysosomal dysfunction in Alzheimer disease neurons 6, suggesting broader roles in neurodegeneration. Low anti-TMED5 serum antibody levels combined with high anti-SKI antibodies predict favorable prognosis in esophageal carcinoma 7, indicating potential diagnostic utility.