Cells down-regulate protein synthesis when stressed to conserve energy and shift resources toward repair. We found that in some mammalian cells, including neurons, stress also resulted in the formatio...

The small ubiquitin-like modifier UFM1 is known to regulate the ribosomal subunit RPL26, but whether other bona fide substrates exist remains debated. This Comment discusses criteria for the experimen...

Nature Reviews Molecular Cell Biology, Published online: 16 February 2026; doi:10.1038/s41580-026-00951-7The small ubiquitin-like modifier UFM1 is known to regulate the ribosomal subunit RPL26, but whether other bona fide substrates exist remains debated. This Comment discusses criteria for the experimental validation of UFM1 substrates.

An orthosteric CSN inhibitor gains nanomolar potency via a molecular-glue mechanism, stabilizing a CSN5–N8–inhibitor complex that confers substrate-dependent inhibition despite weak free-enzyme affinity.

Ubiquitin-binding shuttle proteins are important components of stress-induced biomolecular condensates in cells. Yeast Dsk2 scaffolds proteasome-containing condensates via multivalent interactions wit...

Single-particle tracking experiments in intact cells reveal dynamic co- and post-translational interactions of the TRiC–PFD chaperonin complex with client proteins during in vivo protein folding.

CRISPR screens in iPSC-derived neurons reveal that the E3 ubiquitin ligase CRL5SOCS4 ubiquitinates tau, that CUL5 expression is correlated with resilience in human Alzheimer’s disease, and that electr...

Nature Reviews Molecular Cell Biology, Published online: 09 January 2026; doi:10.1038/s41580-025-00944-yUFMylation, a ubiquitin-like modification, regulates endoplasmic reticulum-associated ribosome quality control by conjugating UFM1 to the ribosomal subunit RPL26, preserving ribosome integrity under stress. This Review explores the structural basis of UFMylation and its emerging functional breadth, and it discusses putative UFMylation substrates.

By studying dynamic folding intermediates on the human ribosome, Pellowe et al. show that newly made domains help each other to fold but do not stably interact until synthesis is complete, avoiding in...