Plasma membrane localized anoctamin 1, 2 and 6 (TMEM16A, B, F) have been examined in great detail with
respect to structure and function, but much less is known about the other seven intracellular members of this
exciting family of proteins. This is probably due to their limited accessibility in intracellular membranous
compartments, such as the endoplasmic reticulum (ER) or endosomes. However, these so-called intracellular
anoctamins are also found in the plasma membrane (PM) which adds to the confusion regarding their cellular
role. Probably all intracellular anoctamins except of ANO8 operate as intracellular phospholipid (PL) scramblases,
allowing for Ca2+-activated, passive transport of phospholipids like phosphatidylserine between both
membrane leaflets. Probably all of them also conduct ions, which is probably part of their physiological function.
In this brief overview, we summarize key findings on the biological functions of ANO3, 4, 5, 7, 8, 9 and 10
(TMEM16C, D, E, G, H, J, K) that are gradually coming to light. Compartmentalized regulation of intracellular
Ca2+ signals, tethering of the ER to specific PM contact sites, and control of intracellular vesicular trafficking
appear to be some of the functions of intracellular anoctamins, while loss of function and abnormal expression
are the cause for various diseases.