Tmem9, or Transmembrane protein 9, is a transmembrane protein involved in multiple biological functions. It is associated with pathways such as the Wnt/β-Catenin signaling pathway, and also has a role in regulating lysosomal acidification by interacting with the v-type ATPase complex. It is highly conserved across species from Caenorhabditis elegans to humans and is widely expressed in various tissues and cells [1,4].

In mice, Tmem9 knockout impairs hepatic regeneration with aberrantly increased adenomatosis polyposis coli (Apc) and reduced Wnt signaling. Mechanistically, Tmem9 down-regulates APC through lysosomal protein degradation via v-ATPase [2]. Genetic ablation of Tmem9 in vitro, ex vivo and in vivo mouse models inhibits colorectal cancer cell proliferation [3]. In addition, knockdown of Tmem9 in hepatoma cells (HepG2 and 7721) inhibits cell proliferation, leads to G1 arrest, induces apoptosis, and decreases cell invasion, migration and adhesion ability [5].

In conclusion, Tmem9 plays crucial roles in various biological processes, especially in liver and intestinal tumorigenesis. Gene knockout mouse models have revealed that Tmem9 is involved in the regulation of Wnt/β-Catenin signaling through APC degradation, and its inhibition can suppress tumorigenesis in relevant cancer types. This indicates the potential of targeting Tmem9 as a therapeutic strategy for liver and colorectal cancers.