Tmed6, short for Transmembrane emp24 protein transport domain 6, belongs to the EMP24_GP25L superfamily and is involved in protein trafficking and secretion [2]. It is selectively expressed in pancreatic islets, with higher levels in α cells than β cells, and may play a role in islet biology, especially in hormone production or secretion. Dysregulation of Tmed6 may be implicated in the development of diabetes [2]. In insects, the silkworm Tmed6 (BmTmed6) is expressed in all stages and tissues of the silkworm [3].

Knockdown of Tmed6 gene expression in Min6 β cells decreased insulin secretion, suggesting its importance in insulin-related functions [2]. In silkworms, reducing BmTmed6 expression significantly decreased the number of eggs laid by female moths, indicating its role in female reproduction, potentially through the dopamine signaling pathway [5]. In renal cell carcinomas, the TMED6-COG8 chimera was found to be dramatically increased in TFE3 translocation RCCs compared with clear cell RCCs and papillary RCCs, suggesting it could be a novel diagnostic marker for Xp11.2 translocation RCCs [1,4].

In summary, Tmed6 plays crucial roles in multiple biological processes. In mammals, it is important for insulin secretion and diabetes-related functions. In insects, it is involved in female reproduction. The discovery of the TMED6-COG8 chimera as a potential diagnostic marker in renal cell carcinomas showcases the significance of Tmed6-related research in disease diagnosis. Studies on Tmed6 using gene-knockdown or knockout models in different organisms have provided valuable insights into its functions in specific biological processes and disease conditions.