In this Review, the authors discuss the physiological and biophysical functions of structurally related TMC, TMEM16 and TMEM63 families, with an aim to elucidate the mechanisms that control ion channel gating and mechanisms for scrambling lipids in the lipid membranes.

XPR1 is the only annotated phosphate exporter protein in humans. Recent studies provide mechanistic clues to its cellular function; three posit non-export mechanisms to regulate phosphate homeostasis, while six present high-resolution cryo-EM data supporting a bona fide phosphate channel mechanism controlled by intracellular phosphate levels.

Aneuploidy is a major cause of embryonic failure and miscarriage. A new study identifies genetic variants of ELL3 associated with miscarriage and discovers a novel role for ELL3 in female meiosis.

Targeted protein degradation is a promising drug discovery approach. A study now describes transferrin receptor targeting chimeras (TransTACS), which lysosomally degrade membrane proteins with potent specificity and efficacy. TransTACs reversibly regulate the tumor-killing activity of CAR-T cells and inhibit drug-resistant EGFR-driven cancers in mice.

Padi and Godek et al. solve cryo-electron microscopy structures of protein phosphatase 2A (PP2A):B55 bound to p107 and Eya3, which, together with nuclear magnetic resonance dephosphorylation experiments, show how PP2A:B55 recruits specific substrates and how it achieves efficient dephosphorylation of phosphosites with high cellular fidelity.

Here, the authors identify SPIN1 as a member of the subcortical maternal complex (SCMC). The SCMC component FILIA protects H3K4me3 reprogramming and zygotic genome initiation by preventing nuclear entry of SPIN1.

Here Ishikawa et al. determine the cryo-electron microscopy structures of the PspCas13b–guide RNA complex alone and in complex with target RNA, as well as that of the dPspCas13b–ADAR2–guide RNA–target RNA complex, thereby providing mechanistic insights into RNA cleavage and editing.

Here, Arkinson et al. reconstitute NUB1-mediated FAT10 degradation by the human 26S proteasome and use biochemistry, cryo-EM and hydrogen–deuterium exchange to show that NUB1 acts as an ATP-independent chaperone to trap partially folded FAT10 for proteasome delivery.

Channelrhodopsins (ChRs) are primary tools for precise optical control over living cells. Structures of a viral ChR, OLPVR1, in closed (1.1 Å) and open (1.3 Å) states reveal the key details of its molecular mechanism.

Naydenova, Boyle and Pathe et al. report that Shigella uses the ubiquitin E3 ligase IpaH1.4 to evade lipopolysaccharide ubiquitylation in infected cells by degrading the host E3 ligase RNF213. Using cryo-electron microscopy, they present the structural basis of this interaction and the mechanism of immune evasion.

We discuss work at the forefront of structural cell biology featured in this issue.