Ano6, also known as TMEM16F, is a member of the anoctamin family. It functions as a phospholipid scramblase, being a major contributor to phosphatidylserine translocation from the inner to the outer leaflet of the plasma membrane, and can also act as an anion/cation channel activated by high Ca2+ concentrations [3]. It is involved in various biological processes and has significance in multiple diseases.

In murine submandibular salivary glands, Ano6 disruption impairs acinar cell regulatory volume decrease (RVD), suggesting it is an essential component of the cell volume-activated, Ca2+-dependent RVD pathway. Also, protein secretion in female glands is affected by Ano6 disruption [6]. In pancreatic ductal adenocarcinoma, CAF-expressed Ano6 is an essential regulator of trogocytosis, promoting cancer cell survival and immune suppression. Blockade of Ano6 antagonizes tumor growth and reverses immune suppression [7]. In SARS-CoV-2 infection, ANO6-mediated phosphatidylserine exposure is critical for viral entry, and ANO6-selective inhibitors can be effective against the infection [4]. In glioma, ANO6 promotes cell proliferation and invasion through regulating the ERK signaling pathway [5]. In gastrointestinal stromal tumors, ANO6 inhibits tumor growth and induces ferroptosis [1]. In breast cancer, ANO6 is an independent prognostic factor, and its elevation is linked to stroma scores and macrophage polarization [2].

In conclusion, Ano6 plays diverse and crucial roles in multiple biological processes and diseases. Studies using gene-knockout models, such as in salivary glands and pancreatic cancer, have revealed its functions in cell volume regulation, protein secretion, tumor growth, and immune regulation. These findings provide insights into potential therapeutic targets for diseases like cancer and viral infections.