Two recent reports presented new evidence that lipid nanoparticles (LNPs) with internal disorder release therapeutic cargo more effectively than highly organized particles. Researchers at the University of Copenhagen used single‑particle, high‑throughput measurements to reveal two LNP subpopulations—organized and amorphous—and found the amorphous particles achieved superior intracellular release. A related presentation at the Biophysical Society meeting showed that disordered internal arrangements reduce the tight electrostatic binding that can trap RNA, improving endosomal release inside target cells. For mRNA and gene therapies, where only ~1–5% of cargo has historically reached the cytosol, the findings suggest formulation strategies should prioritize functional release over maximal encapsulation. The work offers a technical clarification: while encapsulation efficiency matters for dose, therapeutic efficacy can hinge on nanoparticle architecture that favors unbinding and membrane fusion once inside cells.