Tmem72, a transmembrane protein, is involved in normal kidney development and is associated with tumorigenesis in renal cell carcinoma [1,3,4,5]. It has four transmembrane domains (TMDs) and a long C-terminal tail, and is localized on the plasma membrane rather than the outer mitochondrial membrane [1]. The TMDs are crucial for proper protein folding or assembly, while the C-terminal region is essential for protein transport [1].

Immunofluorescence analysis showed its plasma membrane localization [1]. Deletion mutants and unfolded protein response experiments demonstrated the significance of TMDs for folding/assembly [1]. Domain-specific replacement analysis revealed the importance of the C-terminal region in protein transport [1]. Amino acid sequence analysis identified motifs associated with COPII that participate in efficient cellular transport [1]. In bladder cancer, lower TMEM72 expression was associated with better response to atezolizumab [2]. In clear cell renal cell carcinoma (ccRCC), TMEM72 was downregulated, and its down-regulation was potentially linked to metastasis [3,4,5].

In summary, Tmem72 plays a role in protein transport and membrane localization, with implications in kidney development and cancer, especially renal cell carcinoma. The studies on Tmem72 contribute to understanding the pathogenesis of membrane trafficking-associated diseases and the development of renal carcinoma [1].