Proteases and proteolysis in biomolecular condensates.

Protease behavior in biomolecular condensates is governed by the condensate’s physical regime—dynamic liquid, wetting layer, gel-like, or kinetically arrested solid—each constraining protease kinetics.

• Why it matters: Proteases are often studied in dilute solution, but condensates localize enzymes and may create additional reaction compartments, leaving how proteolysis depends on condensate physics unclear.
• What they did: The work argues for regime-aware control of protease diffusion, substrate kinetics, and composition-driven effects, and highlights the need for catalytically inactive controls to distinguish enzyme-catalysed proteolysis from condensate-mediated hydrolysis.
• The result: It proposes that proteolysis can also generate condensate regimes, but direct evidence linking proteases to condensate regulation—and vice versa—remains limited, motivating phase-resolved, falsifiable models.