Homeostatic mechanisms maintain the lipid compositions of organelle membranes. Acute depletion of cholesterol elicited increased synthesis of very long chain sphingolipids, which facilitate lysosome-to–plasma membrane cholesterol trafficking, plasma membrane cholesterol content, and lipid order homeostasis.

Bai et al. discover that the X-linked neurodevelopmental disorder gene product IQSEC2 adopts an autoinhibited conformation that can be released by Ca²⁺ binding, revealing how synaptic activity is directly linked to the ISQEC2 enzymatic activity and why Iqsec2 mutations can have deleterious effect on brain functions. Their results also explain why different mutations of Iqsec2 identified in patients have different and even opposite impacts on the enzyme activity of IQSEC2.

Scott et al. show with ultrastructure expansion microscopy that self-phosphorylation is a major driver of the spatial patterning of PLK4 at the centriole and plays a critical role in selecting a single centriole duplication site.

Pfitzner, Zivkovic, et al. characterize a novel membrane-bound ESCRT-III copolymer initiated by Vps60. They show that Vps60-based copolymers are in vitro spatially and biochemically distinct from classical Snf7-based ESCRT-III filaments. Different behavior of both ESCRT-III filaments in cells furthermore suggests potential diverse functions in vivo.

Legal et al. use cryo-electron tomography to study the tips of motile cilia. They reveal novel structural features of the central pair, expand on the functional role of CEP104/FAP256, and identify potential new proteins that are important for the stability of the ciliary tip.

Drosophila border cells are an excellent model to study fundamental cell behaviors. Torres et al show that elevated and localized Src activity in border cells induces cannibalism of neighboring cells by aberrantly activating phagocytosis with implications for the role of Src in cancer progression.

Metastatic spread of ovarian cancer is associated with multicellular spheroids shed from the primary tumor into the peritoneal cavity. Pawar et al. show that overactive matriptase activates a PAR-2/PI3K/Akt/MMP9 signaling axis to enhance spheroid dissemination and metastasis.