In this Review, Li and Underhill discuss recent advances in understanding the process of phagocytosis. The authors highlight how phagocytosis is integral for innate immune sensing and explain how the ...

The epigenome is sensitive to metabolic inputs and is crucial for aging. Lysosomes act as a signaling hub to sense metabolic cues and regulate longevity. We found that lysosomal metabolic pathways sig...

Lee et al. use an aggregation-prone CLN4 mutant that causes lysosomal damage in neurons and show that in non-neurons, the ubiquitin ligase CHIP prevents CLN4-dependent lysotoxicity via microautophagy.

Join us at the Keystone Symposia on Membrane Dynamics, Repair and Disease, February 2026, in Keystone, with field leaders!

Join us at the Keystone Symposia on Membrane Dynamics, Repair and Disease, February 2026, in Keystone, with field leaders!

ZF5.3 is a mini-protein that escapes endosomes efficiently. Work to understand the underlying mechanism now reveals that ZF5.3 unfolds at pH values lower than 5.5 through protonation of Zn(II)-bound H...

The Tweety homologue TTYH2 is identified as the lipid transfer mediator for APOE-containing lipoproteins.

The cellular response to lysosomal damage involves fine-tuned mechanisms of membrane repair, lysosome regeneration and lysophagy, but how these different processes are coordinated is unclear. Here we ...

Lysosomes break down macromolecules, clear cellular waste and recycle nutrients such as cystine. We describe a novel mechanism whereby JIP4 regulates lysosomal cystine storage by controlling the abundance of cystinosin (CTNS), the transporter responsible for lysosomal cystine efflux. To this end, JIP4, previously characterized as a motor adaptor and kinase signaling scaffold, suppresses TMEM55B-dependent ubiquitylation of CTNS. Loss of JIP4 reduces CTNS protein levels, leading to lysosomal cystine accumulation and lysosomal storage defects that phenocopy loss of CTNS in both human cells and the renal proximal tubules of JIP4 knockout mice. These phenotypes mirror cystinosis, the lysosomal storage disease caused by CTNS loss-of-function. Our findings thus reveal a fundamental process that controls the efflux of lysosomal cystine and has relevance to understanding human disease arising from JIP4 mutations. ### Competing Interest Statement The authors have declared no competing interest. NIH, AG085824, AG062210, R35GM150619 Michael J. Fox Foundation, https://ror.org/03arq3225, ASAP-000580

A study presents EndoMAP.v1, a resource that combines information on protein interactions and crosslink-supported structural predictions to map the interaction landscape of early endosomes.

Intrinsically disordered regions (IDRs) in proteins play essential roles in cellular function. A growing body of work has shown that IDRs often interact with partners in a manner that does not depend ...

Some cancer cells exhibit high loads of reactive iron in lysosomes, and this feature is exploited by using fentomycin-1, a newly developed small molecule, to induce ferroptosis.

Lysosomal phospholipase PLA2G15 was identified as a physiological BMP hydrolase whose activity depends on unique esterification and stereochemistry of BMP and offers a potential therapeutic targe...

After transplantation into the brain of patients with Parkinson’s disease, allogeneic dopaminergic progenitors derived from induced pluripotent stem cells survived, produced dopamine and did not form ...

Wang et al. show the recruitment of the lipid channel protein VPS13C and formation of VPS13C-dependent contacts between endoplasmic reticulum and lysosomes after lysosomal damage.

Autophagy has long been presumed to decline with age, underpinning its designation as a hallmark of ageing. However, emerging evidence challenges this notion, showing tissue-specific variability and, ...

This study uncovers Rab GTPases as evolutionarily conserved signals mediating selective autophagy, targeting damaged mitochondria, lipid droplets, and path

Tambrin et al. show that the Cdc42/Rac GAP ARHGAP12 promotes the flux of macromolecules across tight junctions by suppressing junctional actin assembly and tension via N-WASP and the Arp2/3 complex. T...