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  • Sphingolipids are a heterogeneous group of lipids with important roles in membrane form and function, cell signalling, and development. This Review discusses the regulation of sphingolipid metabolism at the subcellular and organismal levels and explores the therapeutic potential of targeting sphingolipids in human diseases.

    • Andrew Kuo
    • Timothy Hla
    Review Article
  • Endosomes function as sorting stations that segregate cargo proteins into endosomal carriers, enabling their distribution to subcellular target compartments. Increasingly detailed structural insights have revealed how proteins, such as sorting nexins, assemble on endosomal membranes to form a coat that facilitates the formation and detachment of tubular carriers.

    • Navin Gopaldass
    • Kai-En Chen
    • Andreas Mayer
    Review Article
  • Kawaguchi et al. identify a chromatin code based on repressive histone 3 lysine 27 trimethylation (H3K27me3) that serves as a segment-specific positional marker in connective tissue cells of axolotls, enabling correct patterning during limb regeneration.

    • Lisa Heinke
    Research Highlight
  • Senescent cells have complex and important roles in cancer and ageing, but they are quite rare and difficult to characterize in tissues in vivo. In this Expert Recommendation, the SenNet Biomarkers Working Group discusses recent advances in detecting and characterizing cellular senescence and provides recommendations for senescence markers in 14 human and mouse tissues.

    • Vidyani Suryadevara
    • Adam D. Hudgins
    • Nicola Neretti
    Expert Recommendation
  • Biomolecular condensates are emerging as hubs of splicing regulation. This Review discusses the modulation of condensate functions through alternative splicing, regulation of (co-transcriptional) splicing at condensates and the involvement of these condensates in human diseases.

    • Jimena Giudice
    • Hao Jiang
    Review Article
  • Verheyen and Gottardi revisit two seminal papers by the Basler, Peifer and Clevers labs elucidating the role of nuclear β-catenin in Wnt signal transduction through its interaction with TCF at Wnt target genes.

    • Esther M. Verheyen
    • Cara J. Gottardi
    Journal Club
  • Claire Durrant reminds us of the importance of studying the physiological roles of proteins and their aggregates to understand their roles in disease and inform therapies, discussing a 2008 paper on amyloid-β from the Arancio lab.

    • Claire S. Durrant
    Journal Club
  • Stephanie Moon discusses findings that revealed that ribosome stalling can lead to the suppression of translation initiation in the brain, delaying the onset of neurodegeneration.

    • Stephanie L. Moon
    Journal Club
  • Oxidation–reduction (redox) reactions involving reactive oxygen, nitrogen and sulfur species are vital for life, but excessive oxidant levels contribute to ageing and diseases. This Review explores cellular dynamics of redox homeostasis, such as responses to oxidative and reductive stresses and intracellular and intercellular redox communication pathways.

    • Helmut Sies
    • Ryan J. Mailloux
    • Ursula Jakob
    Review Article
  • During embryonic epithelial–mesenchymal transition, epithelial cells undergo substantial phenotypic changes and acquire migration capacity. This Review compares embryonic and adult non-cancer EMTs and discusses the role of EMTs in adult tissue repair and fibrosis, highlighting therapeutic opportunities to modulate EMT to reduce fibrosis and promote repair.

    • Khalil Kass Youssef
    • M. Angela Nieto
    Review Article
  • This article reviews the current landscape of targeted protein degradation approaches and how they have parallels in biological processes. The authors also outline the ongoing clinical exploration of novel degraders and provide some perspectives on the directions the field might take.

    • Jonathan M. Tsai
    • Radosław P. Nowak
    • Eric S. Fischer
    Review Article
  • Robert Parton and colleagues discuss novel evidence on the role of dynamin in caveolar endocytosis, which calls into question established models of dynamin-mediated fission.

    • Robert G. Parton
    • Justin W. Taraska
    • Richard Lundmark
  • Reversible S-palmitoylation regulates gasdermin D cleavage, membrane translocation and pore formation to control pyroptosis following bacterial infection.

    • Lisa Heinke
    Research Highlight