ANO6, also known as TMEM16F, is a member of the TMEM16 protein (anoctamin) family. It functions as a phospholipid scramblase, contributing to phosphatidylserine translocation from the inner to the outer leaflet of the plasma membrane, and may also act as an anion/cation channel activated by high Ca2+ concentrations [3]. It is involved in multiple biological processes and is associated with various diseases.

In gastrointestinal stromal tumors (GISTs), ANO6-plasmid inhibits cell proliferation, induces apoptosis, pyroptosis, and ferroptosis, suggesting its potential as a therapeutic target [1]. In breast cancer, lower ANO6 expression is observed in cancer tissues, and its overexpression predicts poor overall survival, indicating it as an independent prognostic factor and potentially a treatment target. It may affect cancer progression via stroma-related pathways and macrophage polarization [2]. In glioma, ANO6 promotes cell proliferation and invasion through regulating the ERK signaling pathway [4]. Also, in pancreatic ductal adenocarcinoma, ANO6 in cancer-associated fibroblasts is crucial for lipid transfer to cancer cells via trogocytosis and for immunosuppression, and its blockade may be a new therapy strategy [5]. In Alzheimer's disease cells, ANO6 targets TMEM30A to regulate endoplasmic reticulum stress-induced lipid peroxidation and ferroptosis [6].

In conclusion, ANO6 has diverse functions in multiple biological processes and diseases. Studies using various models, though not specifically KO/CKO mouse models in the provided references, have revealed its roles in cancer development, immune-related processes, and neurodegenerative disease-associated mechanisms. Understanding ANO6 provides potential therapeutic directions for treating these diseases.

References:

1. Wang, Hao, Zhao, Wei, Wang, Daorong, Chen, Jin. 2024. ANO6 (TMEM16F) inhibits gastrointestinal stromal tumor growth and induces ferroptosis. In Open medicine (Warsaw, Poland), 19, 20240941. doi:10.1515/med-2024-0941. https://pubmed.ncbi.nlm.nih.gov/38756246/

2. Tang, Long-Huan, Dai, Min, Wang, Dong-Hai. . ANO6 is a reliable prognostic biomarker and correlates to macrophage polarization in breast cancer. In Medicine, 102, e36049. doi:10.1097/MD.0000000000036049. https://pubmed.ncbi.nlm.nih.gov/37960776/

3. Pedemonte, Nicoletta, Galietta, Luis J V. . Structure and function of TMEM16 proteins (anoctamins). In Physiological reviews, 94, 419-59. doi:10.1152/physrev.00039.2011. https://pubmed.ncbi.nlm.nih.gov/24692353/

4. Xuan, Zhao-Bo, Wang, Ye-Ji, Xie, Jun. 2019. ANO6 promotes cell proliferation and invasion in glioma through regulating the ERK signaling pathway. In OncoTargets and therapy, 12, 6721-6731. doi:10.2147/OTT.S211725. https://pubmed.ncbi.nlm.nih.gov/31692479/

5. Ogier, Charline, Solomon, Akino Mercy Charles, Lu, Zhen, Cukierman, Edna, Astsaturov, Igor. 2023. Trogocytosis of cancer-associated fibroblasts promotes pancreatic cancer growth and immune suppression via phospholipid scramblase anoctamin 6 (ANO6). In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.09.15.557802. https://pubmed.ncbi.nlm.nih.gov/37745612/

6. Wang, Ying, Li, Penghui, Liang, Yonghan, Wang, Dandan. 2025. ANO6 Targets TMEM30A to Regulate Endoplasmic Reticulum Stress-Induced Lipid Peroxidation and Ferroptosis in Alzheimer's Cells. In Cell biochemistry and biophysics, , . doi:10.1007/s12013-025-01748-9. https://pubmed.ncbi.nlm.nih.gov/40221538/