Proteins in the Transmembrane Channel-Scramblase (TCS) superfamily share an evolutionarily conserved ability to permeate ions and phospholipids, challenging distinctions between ion channels and lipid scramblases.

While activated by a common mechanism, both functions in TMEM16F - lipid scrambling and ion conduction - are likely mediated by alternate protein conformations that are at equilibrium in the ligand-bound state.

Single-particle cryo-EM and electrophysiology studies of the chloride channel TMEM16A reveals the structural basis for anion conduction and uncover its relationship to lipid scramblases of the same family.

TMEM16F shifts its ion selectivity in response to change of intracellular Ca²⁺, membrane potential and ionic strength.

Structures of a TMEM16 phospholipid scramblase reveal that its Ca²⁺-dependent activation entails global conformational changes and how these rearrangements affect the membrane to enable transbilayer lipid transfer.

A concerted approach employing equilibrium and biased molecular simulations, electrophysiology, mutagenesis, and functional assays reveals, in atomic details, the mechanism and pathway for transport of phospholipids and ions by a lipid scramblase.

The structural relationship between TMC and TMEM16 proteins provides insight into the structure and functional mechanisms of the mechanotransduction channel complex in hair cells.

The identification of four acidic amino acids as potential calcium-binding residues in the TMEM16A calcium-activated chloride channel furthers the molecular understanding of this ion channel family.

A newly characterized calcium-activated chloride channel has been implicated in the immune system of Drosophila, shedding light on an enigmatic family of transmembrane proteins that are ubiquitous in nature.

A previously unknown calcium channel in human placental trophoblasts provides a calcium source for activating TMEM16F lipid scramblase that flip-flops phospholipids on cell surface, demonstrating a physiological mechanism that helps to understand how lipid dynamics regulates cell fusion.