["Acta Physiologica, Volume 242, Issue 6, June 2026. ", "\nABSTRACT\n\nAim\nCa2+‐activated Cl– conductances are present in many cell types and are important for regulating membrane potential as well as other cellular functions. TMEM16A is widely accepted as the principal molecular basis for Ca2+‐activated Cl– conductances, but also members of the bestrophin family may be important for some Ca2+‐activated Cl– conductances.\n\n\nMethods\nIn this review, we discuss the possibility that members of the two families, bestrophins and TMEM16A, may interact.\n\n\nResults\nIn the cardiovascular system, the evidence is strongest. Here (1) TMEM16A and bestrophin‐3 are closely located in the membrane, (2) TMEM16A may regulate the expression of bestrophin‐3, and (3) a cGMP dependent Ca2+‐activated Cl– conductance is dependent on both TMEM16A and bestrophin‐3. Outside the cardiovascular system, both TMEM16A and bestrophins are implicated in the regulation of cellular Ca2+ independently of membrane potential, and both proteins are importantly associated with inflammation and pain transmission. However, it seems that little testing of a direct interaction of TMEM16A and bestrophins has been published.\n\n\nConclusion\nWe conclude that there is evidence for direct interaction between TMEM16A and bestrophins in the cardiovascular system, and it will be important to determine whether similar interactions extend to other tissues.\n\n"]