Molecules and Cells 2025, highlights from molecules to organisms.

Hyerim Park: Writing – original draft. Seung-Jae V. Lee: Writing – review & editing.

Cancer and tumor immunity emphasizes immune context and genome-encoded vulnerabilities as determinants of therapy response. The functions of human γδ T cells in the tumor microenvironment are summarized and discussed for how these cells can be used to improve cancer immunotherapy ( Park and Lee, 2025b ). Targeting histone demethylases is reviewed as a strategy for cancer therapy ( Shin et al., 2025b ), and omics data provide stratification parameters for colorectal cancer ( Fatfat et al., 2025 ) along with an overview of therapeutic principles ( Lee, 2025 ). Identification of a tumor-restraining mucosal fibroblast subpopulation extends stromal cell biology in colorectal cancer ( Ku et al., 2025b ). Tumor-derived CD84 links nonhomologous DNA end-joining regulation to acute myeloid leukemia growth ( Li et al., 2025 ). Ectopic expression of membrane-bound interleukin-7 (IL-7) in tumor cells promotes antitumor immune responses in colon carcinoma ( Shin et al., 2025a ). Deficient chaperone-mediated autophagy in macrophages exacerbates colitis and colitis-associated tumorigenesis in mice ( Zhu et al., 2025 ).

Genome-level instability acts as a prognostic indicator in cancer through base excision repair genes ( Kim et al., 2025a ), while systematic decoding of genomic rearrangements enables the identification of oncogenic factors ( Seo et al., 2025 ). Chromatin-associated regulators extend genome regulation into pathology, including Microrchidia family CW-type zinc finger 2 (MORC2)-related disease mechanisms ( Zhao and Miao, 2025 ). Defects in RNA quality control and processing contribute to disease phenotypes. Suppressors with morphogenetic effect on genitalia family member 1 (SMG1)-associated defects in nonsense-mediated mRNA decay (NMD) are tested in a human pluripotent stem cell model ( Lee et al., 2025a ). Dysregulated RNA-binding proteins and alternative splicing expand the neurodevelopmental context ( Jeong et al., 2025 ), while autism spectrum disorder genomics provides a precision-diagnosis approach ( Kim and An, 2025 ). RNA-associated nuclear condensates position nuclear organization as a regulatory site that determines RNA fate ( Ku et al., 2025a ). Genetic systems bridge genome-to-phenotype inference through expression quantitative trait loci systems for complex disease mechanisms ( Hong et al., 2025a ).

None.

Signaling specificity is determined by modifications, ion-lipid messengers, and phosphatase-mediated regulation. Protein- O -fucosylation of coreceptors is discussed as a potential requirement for Nodal signaling in Xenopus laevis ( Kim et al., 2025f ). Calcium ATPases and phosphoinositides connect Ca 2+ homeostasis to pathology and therapeutic strategies ( Gu et al., 2025 ). The protein phosphatase 2A B56 regulatory subunit underlies phosphatase-mediated regulation of cell division ( Oh et al., 2025b ), and Iroquois signaling regulates broad developmental and disease-related processes ( Goutam et al., 2025 ). eIF2α phosphorylation mitigates the activation of cell death pathways, including ferroptosis, by preserving glutathione and nicotinamide adenine dinucleotide phosphate hydrogen homeostasis during endoplasmic reticulum (ER) stress ( Le et al., 2025a , Le et al., 2025b ). A study characterizes the eIF2α phosphorylation-transcription factor 4 (ATF4) axis, which induces ATF4-dependent transcriptional changes that mitigate mitochondrial impairment during ER stress ( Le et al., 2025a , Le et al., 2025b ). Pentraxin 3 deficiency ameliorates streptozotocin-induced pancreatic toxicity by regulating ER stress and β-cell apoptosis ( Kim et al., 2025d ). Metabolic regulation is characterized by cholesterol sulfate as a negative regulator of cholesterol homeostasis ( Nam et al., 2025 ) and by dysregulation of iron metabolism that causes ferroptosis in pulmonary fibrosis ( Jiang et al., 2025 ). Serine hydroxymethyltransferase biology links 1-carbon metabolism to broad physiology and pathology ( Zhang et al., 2025 ). Structural studies include cryo-electron microscopy structures of bestrophin 1 ( Kim et al., 2025b ) and conformational transitions that influence carbonic anhydrase catalytic activity ( Lim et al., 2025b ). The crystal structure of γ-carbonic anhydrase from Aeribacillus pallidus indicates that the amino acid composition at the active site differs from that of the prototypic γ-carbonic anhydrase, which explains the lack of measurable CO 2 hydration activity ( Choi and Jin, 2025 ). Artificial intelligence (AI)-based modeling is discussed for metalloprotein studies ( Kim et al., 2025e ).

Immunity studies describe innate sensing and immune cell differentiation in infection and inflammation. Charge-dependent localization of Toll-like receptor 5 (TLR5) at the plasma membrane is explained by a polybasic C-terminal region that is required for surface retention, distinguishing TLR5 from TLR9 internalization ( Huh et al., 2025 ). Pattern recognition receptor (PRR)-to-inflammasome pathways organize innate immunity mechanisms ( Oh et al., 2025c ). microRNA-196a links forkhead box O1 (FOXO1)-mediated regulation to B cell apoptosis ( Kim et al., 2025c ). Early growth response 2 (Egr2)-dependent monocyte-derived dendritic cells are connected to natural killer cell immunoregulation during acute Listeria infection ( Ashraf et al., 2025 ). Inflammatory mechanisms in endometriosis link the pathological state to infertility ( Park et al., 2025b ). Secreted phosphoprotein 1 (SPP1)-mediated regulation is described as a factor of disease progression ( Jung et al., 2025 ), and hereditary hearing loss is assessed by employing the genetics of semaphorin 3F (SEMA3F) variants ( Joo et al., 2025 ). Neurodegeneration is reported through cellular quality control and therapeutic intervention, encompassing microglial replacement in Alzheimer’s disease ( Bang and Yoo, 2025 ). Parkinson’s disease is covered through therapeutic strategies ( Kim and Lee, 2025 ) and autophagic signatures in peripheral blood mononuclear cells from Parkinson’s disease patients ( Lee et al., 2025e ), and microbiota-derived inhibition of α-synuclein fibrillation ( Shiraz et al., 2025 ). Gene therapy for hearing loss ( Jang et al., 2025 ) and optogenetic regulation of phase separation ( Park and Kim, 2025a ) provide therapeutic strategies for sensory and neurodegenerative pathologies.

Host-microbe communication regulates physiological processes through pathways that extend beyond cell-intrinsic regulation. Intestinal bacteria-derived extracellular vesicles establish an interkingdom signaling axis in metabolic dysfunction-associated steatotic liver disease ( Qin et al., 2025 ). Sensory and behavioral regulation is addressed through dietary salt-induced taste desensitization via receptor internalization and through ionotropic receptor-mediated arachidic acid perception and food avoidance behavior in Drosophila melanogaster ( Jin et al., 2025 , Pradhan et al., 2025 ). Plant studies describe cyclotide-based therapeutic scaffolds ( Hyun, 2025 ), for synthetic biology ( Koo et al., 2025a ), and natural product biosynthesis prediction via READRetro ( Kwak et al., 2025b ). The disordered effector RipAO destabilizes microtubule networks during plant-pathogen interactions ( Jeon et al., 2025 ). Organism-level studies are represented by genome-wide inference of candidate factors linked to life expectancy in dogs ( Ko et al., 2025 ) and by a Drosophila model that links metabolism to memory ( Nath and Lee, 2025 ).

Cell-state mechanisms are characterized by transcription factor networks in prostate cancer progression ( Lee and Lee, 2025 ) and by tumor suppressor p53-mediated metabolic pathways ( Koo et al., 2025b ). Receptor-interacting protein kinase-3 is discussed as a key factor in necroptosis with emerging roles in cancer ( Morgan and Kim, 2025 ). Developmental and regenerative processes include RNF220 isoform requirements during muscle differentiation ( Choi et al., 2025b ) and stem cell-niche interactions in lung regeneration ( Lee et al., 2025c ). Systemic regulation is reflected in postingestive nutrient sensing as an organism-wide regulatory system ( Lee et al., 2025b ). Dual inhibition of SMAD2/3 and SMAD1/5/8 supports pluripotent stem cell maintenance ( Puspita et al., 2025 ).

During the preparation of this work, the authors used ChatGPT-5.2 (OpenAI) to improve language clarity of the manuscript. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.

None.

Technique-oriented MiniResources and Review/Minireview papers include method papers and practical guides. Method development covers the DNA curtain, a high-throughput single-molecule technique that aligns many DNA molecules for parallel fluorescence imaging of DNA-protein interactions ( An et al., 2025 ), as well as single-molecule imaging approaches for transcriptional regulation ( Choi and Baek, 2025 ). Additional resources provide optimization of fluorescence resonance energy transfer (FRET) imaging in Arabidopsis thaliana protoplasts ( Choi et al., 2025a ) and adeno-associated virus (AAV)-based gene delivery to the brain ( Han et al., 2025 ). Practical protocols include immune cell isolation ( Park and Lee, 2025a ), murine T cell isolation and activation ( Lim et al., 2025a ), measurement of mitochondrial membrane potential, reactive oxygen species, calcium ( Park and Kang, 2025 ), and plasma membrane protein detection ( Roh et al., 2025 ). Furthermore, Caenorhabditis elegans survival ( Kwon and Lee, 2025 ), health parameter assays ( Hwang et al., 2025 ), and strain ordering ( Park et al., 2025c ), together with mouse research practices ( Haque et al., 2025 ), establish essential experimental resources. Brief technical guides provide protocols for western blot ( Ha et al., 2025 ), gene cloning ( Hong et al., 2025b ), immunostaining ( Park et al., 2025a ), ferroptosis detection ( Thi Nghiem et al., 2025 ), plant TurboID labeling ( Park and Kim, 2025b ), and C. elegans imaging ( Min et al., 2025 ). Bioinformatics platforms provide Transcriptome-wide High-throughput RNA-seq Analysis Integrated System for RNA-seq analysis ( Heo and Um, 2025 ), GOREA for functional enrichment ( Lee et al., 2025d ), and SimpleViz for data visualization ( Oh et al., 2025a ). Behavioral analysis is supported by zebrafish-specific software ( Ranasinghe and Cha, 2025 ). Scientific correspondence addresses the characterization of FAM19A5 as an adipokine ( Kong, 2025 , Kwak et al., 2025a ). In conclusion, the manuscripts published in Molecules and Cells in 2025 advance our understanding of molecular mechanisms underlying biological processes at the cellular and organismal levels.