Tmem72, a transmembrane protein, is involved in normal kidney development and has implications in tumorigenesis, especially in renal cell carcinoma [1,3,4,5]. It has four transmembrane domains (TMDs) and a long C-terminal tail, localizing on the plasma membrane rather than the outer mitochondrial membrane [1]. Efficient membrane trafficking mediated by Tmem72 is crucial for cells to maintain normal function, and its malfunction may contribute to membrane trafficking-associated diseases [1].

Research shows that TMDs of Tmem72 are needed for proper protein folding or assembly, while the C-terminal region is essential for protein transport [1]. Specifically, the motifs 132KRKKRK137 and 139APEVLA144 in the C-terminal region are associated with COPII and cooperate with membrane trafficking [1]. In bladder cancer, lower TMEM72 expression is associated with better response to atezolizumab, and in clear cell renal cell carcinoma (ccRCC), TMEM72 is downregulated, potentially related to prognosis [2,3]. Also, in ccRCC, TMEM72 down-regulation may be linked to metastasis [4,5].

In conclusion, Tmem72 plays a significant role in normal kidney development and is closely associated with renal carcinoma. Its function in protein folding, assembly, and transport, as well as its differential expression in cancer, provides insights into the pathogenesis of kidney-related diseases. The study of Tmem72 helps in understanding the biological processes related to membrane trafficking and the development of renal cancers.