This Perspective discusses the emerging cellular roles of lysine lactylation, with a focus on the lactyl-CoA-independent pathway, and highlights the potential strategies of targeting lactylation for the treatment of associated human diseases.

This Review discusses the role of phosphatidylinositol phosphates and their modifying enzymes in modulating cell motility and adhesion and emphasizes the potential of targeting the associated pathways for therapeutic benefit.

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, in some cases, age-related increases in autophagic activity. Understanding these dynamics is vital for targeted therapeutic strategies.

Lysosomal dysfunction is emerging as a common pathogenic mechanism underlying normal ageing and many age-related diseases. Lysohormesis, the triggering of beneficial adaptations by mild lysosomal stress leading to increased lysosomal function and cellular stress resilience, could provide a common solution to many age-related issues.

Kim et al. show that NAD⁺ kinase 2 serves as a source of mitochondrial NADPH to support mitochondrial fatty acid synthesis, protein lipoylation and mitochondrial oxidative metabolism.

Wang, Wilfahrt and colleagues show that phosphoethanolamine, a phospholipid intermediate, is enriched in tumour interstitial fluid and induces T cell dysfunction, in part by depleting diacylglycerol and dampening T cell receptor signalling.

Wang, Wang, Pan and colleagues uncover a C864–C869 disulfide linkage stimulated by viral RNA that drives RIG-I activation, phase separation and stimulates downstream innate immune signalling.

Han et al. report the existence of neural stem cells (NSCs) outside the central nervous system and show that these peripheral NSCs display features similar to brain NSCs, including the ability to differentiate into mature neurons.

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.

Taniguchi et al. structurally analyse nuclear pore complex architecture in situ during differentiation, which is associated with mechanical constraints on the nuclear envelope. They link nuclear pore complex elasticity to nuclear envelope integrity in differentiation.

Integrating protocols.io into the submission process makes collaborative protocol sharing and peer review seamless for authors and referees in a step towards open science.

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, in some cases, age-related increases in autophagic activity. Understanding these dynamics is vital for targeted therapeutic strategies.

Lysosomal dysfunction is emerging as a common pathogenic mechanism underlying normal ageing and many age-related diseases. Lysohormesis, the triggering of beneficial adaptations by mild lysosomal stress leading to increased lysosomal function and cellular stress resilience, could provide a common solution to many age-related issues.