Anoctamin-9 (ANO9)

Anoctamin-9 (ANO9) is a transmembrane protein belonging to the TMEM16/anoctamin family, functioning primarily as a Ca²⁺-activated nonselective cation channel and phospholipid scramblase[1][4]. It forms part of cellular mechanisms regulating ion transport, membrane phospholipid asymmetry, and Ca²⁺-dependent signaling. Structurally, ANO9 has eight predicted transmembrane domains[1]. ANO9 is critical for the initial rise in cytosolic Ca²⁺ during T-cell activation, modulates the activity of plasma membrane Ca²⁺-ATPases, and interacts with scaffolding proteins such as DLG1 for proper cellular localization[3]. In cancer, ANO9 acts as a tumor suppressor, with reduced expression linked to poorer outcomes and higher recurrence rates in colorectal cancer patients[2][4]. It does not display calcium-activated chloride channel activity but instead regulates activity of other family members (such as ANO1), affecting proliferation, invasion, and ion signaling in cancer and immune cell contexts[2][3][4]. Its expression is associated with several diseases, including certain cancers, macular degeneration, immune-related disorders, and may contribute to infectious disease pathways[4]. No currently approved drugs directly target ANO9, but its molecular functions offer opportunities for novel therapeutic and biomarker strategies, especially in oncology and immunology[2][3][4].

Other names

Anoctamin-9ANO9TMEM16JTransmembrane protein 16JPIG5TP53I5Tumor protein p53-inducible protein 5p53-induced gene 5 protein

Modulation of Ca²⁺ entry and signaling (potential mechanism for immune modulation and anti-proliferative activity); Inhibition of other anoctamin family members (e.g., ANO1, which is linked to cancer progression)