Condensatopathies as a mechanistic framework for disease and integrated theranostic intervention.
The spatial organization of the cell relies on biomolecular condensates formed via liquid-liquid phase separation (LLPS).
APA
Li X, Wang H, et al. (2026). Condensatopathies as a mechanistic framework for disease and integrated theranostic intervention.. Theranostics, 16(6), 2684-2704. https://doi.org/10.7150/thno.127750
MLA
Li X, et al.. "Condensatopathies as a mechanistic framework for disease and integrated theranostic intervention.." Theranostics, vol. 16, no. 6, 2026, pp. 2684-2704.
PMID
41510158
Abstract
The spatial organization of the cell relies on biomolecular condensates formed via liquid-liquid phase separation (LLPS). The dysregulation of this physicochemical order drives a growing class of human pathologies. Here, we champion the unifying term "Condensatopathies" and establish a rigorous framework for their classification based on three core criteria: genetic/environmental triggers, demonstrable biophysical defects, and causal toxicity. We synthesize the pathogenic landscape into two distinct yet interconnected mechanisms: Loss-of-Function (LOF), where essential condensates fail to form or harden; and Toxic Gain-of-Function (TGOF), characterized by the formation of aberrant, often solid-like aggregates or oncogenic hubs that hijack cellular machinery. By analyzing representative cases-from the biophysical maturation of TDP-43 in neurodegeneration to the chromatin hijacking by NUP98 fusions in leukemia-we reveal how the loss of "tunable metastability" underpins these disorders. Furthermore, we review how emerging technologies like optogenetics and cryo-ET are decoding these mechanisms. Finally, we propose an integrated "See-and-Treat" theranostic paradigm, utilizing the unique material properties of condensates to design specific diagnostic probes and "molecular scalpels" for precision intervention.
MeSH Terms
Humans; Theranostic Nanomedicine; Animals; Neurodegenerative Diseases; Precision Medicine; DNA-Binding Proteins
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