Two independent reports presented converging evidence that structural heterogeneity in lipid nanoparticles (LNPs) can improve intracellular cargo release. University of Copenhagen researchers used a high‑throughput single‑particle assay to show that amorphous, disorganized LNP subpopulations released RNA more effectively than highly organized particles, providing a potential path to boost functional delivery efficiency. Separately, research on LNP internal disorder and cryo‑EM/biophysical advances suggest delivery efficiency depends on particle organization and charge distribution. These findings challenge the prevailing optimization dogma that tighter packing always improves payload protection. For developers of mRNA vaccines and therapeutics, the results point to new quality‑by‑design variables: population heterogeneity, subpopulation characterization, and controlled disorder to improve endosomal escape and payload bioavailability. LNPs are the lipid‑based carriers that encapsulate nucleic acids for cellular delivery; improving their release kinetics is critical for therapeutic efficacy.