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Ion channels, transporters and lipid scramblases are integral membrane proteins that play vital roles in enabling movement of ions, nutrients and lipids across biological membranes. We use a combination of biophysical, structural and bioinformatic approaches to elucidate the structural and mechanistic underpinnings of ion and lipid transport. We focus on two membrane protein families, the CLC channels and transporters and the TMEM16 channels and scramblases.