Exosomes are derived from endosomal compartments with an ill-defined molecular identity and whose trafficking steps to secretion are poorly understood. Using advanced imaging approaches, the authors identified these compartments as pre-lysosomal endosomes that require dynamic membrane contact sites with the endoplasmic reticulum to induce a prosecretory cascade of small-GTPases.

Increased cholesterol uptake by the LDLR contributes to the immunometabolic response of activated CD8⁺ T cells through the modulation of lysosome–mTORC1 axis. This finding paves the way for cell-selective targeting of the LDLR to boost CD8-dependent immune response.

Lim et al. investigate the internalization mechanism of the antigen presenting molecule, MR1. Recognition of a conserved atypical motif in MR1’s cytoplasmic tail by AP2 defines the endocytosis rate and duration of MR1–metabolite cell surface display, functioning as the “off” switch for MR1 presentation.

ARL3 mutations disrupt protein import into cilia causing Joubert syndrome (JBTS). Using Chlamydomonas, Liu et al. show that ARL3 recruits the BBSome to pass the transition zone for ciliary retrieval, providing a mechanistic explanation for why JBTS phenotypically overlaps with Bardet-Biedl syndrome.

Laidlaw et al. show nutrient transporters rapidly internalize to an early endosome population. Substrate withdrawal triggers endosomal recycling of transporters from endosomes back to the surface in a pathway that relies on ubiquitination of the ESCRT protein Ist1 and the associated factors Cdc48 and Npl4.

Phagocytosis by different cell types is essential for tissue homeostasis and function. This study identifies a Cdc42-based dual effector signaling mechanism that drives actomyosin remodeling and, thereby, internalization of phagocytic ligands in retinal pigment epithelial cells.

Lipid droplets (LDs) can exhibit liquid crystalline sterol-esters in vivo, but the mechanisms governing this are unclear. Rogers et al. describe how yeast glucose restriction drives triglyceride lipolysis that promotes liquid crystalline phase transitions within LDs. They also investigate how these phase transitions alter the LD proteome.