Proteomic and transcriptomic profiling on hiPSC-derived midbrain dopaminergic neurons with pathological α-synuclein burden reveals defective Sec61A interactions and co-translational translocation of E...

Park et al. describe problems that plague the analysis of ribosome specialization, as well as ways to address them to guide experimentation in the field.

Chromosomal translocations leading to the fusion of tropomyosin receptor kinases (TRKs) with diverse partner proteins have been identified as oncogenic drivers in many adult and pediatric cancers. Whi...

Clearance of arrested nascent polypeptides resulting from ribosomal stalling is essential for proteostasis. Stalled endoplasmic reticulum (ER)-bound ribosomes are marked by ubiquitin-fold modifier 1 (...

Here, Deol et al. use genetic screens in gene-edited reporter cell lines to identify regulators of ferroptosis suppressor protein 1 (FSP1) expression and stability. They show that vitamin B2 metabolis...

After performing a focused CRISPR–Cas9 screen, Skafar et al. identify riboflavin (vitamin B2) as a regulator of FSP1 stability that modulates phospholipid peroxidation and ferroptosis sensitivity in c...

CRISPR–Cas9 screening identifies CLCC1 as a factor that increases neutral lipid flux to prevent hepatic steatosis and promotes nuclear pore complex assembly by promoting membrane bending and fusi...

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...

Nuclear protein homeostasis relies on proteasome import into the nucleus. Here the authors identify how assembled human proteasomes are transported across the nuclear pore complex and reveal a mechani...

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...

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...

imageimageOocytes are long-lived cells that require specialized adaptations to maintain their fitness. This study shows that human oocytes display low lysosomal, proteasomal, and mitochondrial activity, which declines further during oocyte ...

This Review examines recently gained insights into the roles of ESCRT complexes in viral infection, immunity, cancer and neurological disease.

Nature Structural & Molecular Biology - UFMylation-dependent quality control of ER-stalled ribosomes

FSP1 is an FAD-dependent oxidoreductase that uses NAD(P)H to regenerate the reduced forms of lipophilic quinone antioxidants, such as coenzyme Q10 ...

In this study, we show that Pex30 dysferlin domain binds PA through its two hydrophobic regions adjacent to beta sheets. We propose that, PA, a precursor f

N-glycosylation of secretory pathway proteins in the ER is crucial for their maturation and quality control. Recent insights into the enzymes and chaperones that facilitate N-glycosylation have expand...

Structures of stalled ER-bound 60S ribosomal subunits identify cooperative interaction between UFMylation and RQC machineries.