Intracellular vesicle trafficking is the principal transportation system in eukaryotic cells, and is considered to be involved in a variety of processes related to cell proliferation. A protein named alpha-taxilin has been identified as a binding partner of the syntaxin family, which coordinates intracellular vesicle trafficking. To clarify the role of alpha-taxilin in renal cell carcinoma (RCC), we investigated alpha-taxilin protein expression in clear cell RCC tissues. We analyzed alphataxilin protein in matched sets of tumor and non-tumor tissues from the surgical specimens of 52 Japanese RCC patients by Western blotting. We also studied the relation between alpha-taxilin protein expression in tumor tissues and various clinicopathological features. The alpha-taxilin protein level was higher in tumor tissues than in non-tumor tissues (P < 0.05). Increased expression of alpha-taxilin protein in primary tumors was related to local invasion (P < 0.001), pathological vessel invasion (P < 0.001), and metastasis (P < 0.0001). Kaplan-Meier plots of survival for patients with low versus high alpha-taxilin expression revealed that high expression in tumor tissues was associated with shorter overall survival in all patients (P < 0.05) and with shorter disease-free survival in patients without metastasis (P < 0.01). These findings suggest that alpha-taxilin influences the metastatic and invasive potential of RCC.Intracellular vesicle trafficking is the principal transportation system in eukaryotic cells, and vesicle trafficking is thought to be involved in various processes related to cell proliferation. Abnormal proliferation is the hallmark of cancer. Recently, a protein named alpha (α)-taxilin was identified as a binding partner of the syntaxin family, which is involved in the coordination of intracellular vesicle trafficking (26). The taxilin family has at least three members-α-, beta (β)-, and gamma (γ)-taxilin-and α-taxilin possesses an extremely long coiled-coil region and interacts with syntaxin family members localized on the plasma membrane, but not with those localized on intracellular organelles (26, 28). There is evidence that the taxilin family is involved in the transfer of vesicles delivered to the plasma membrane (26, 28). However, the precise influence of the taxilin family on the functions of the syntaxin family remains to be fully elucidated, and the actual role of α-taxilin in intracellular vesicle trafficking is also unknown. In addition to providing information about the molecular mechanisms involved, examination of the physiological and pathophysiological functions of taxilin should improve our understanding about the role of this family of proteins. We recently reported that α-taxilin protein is significantly upregulated in proliferating neural stem cells during embryonic development in the rat (37). In addition, Oba-Shinjo et al. recently reported that