Introduction: Red-light Accelerated PhotoActivation (RAPA) of melittin-functionalized mRNA lipid nanoparticles is a novel strategy to enhance mRNA delivery. This approach uses tissue-penetrant red light to spatiotemporally activate melittin’s lytic activity within endosomes, enabling efficient mRNA escape into the cytosol. RAPA enables on-demand cytosolic release of mRNA with minimal off-target effects, addressing the endosomal barrier in mRNA therapeutics. By enhancing endosomal escape, this strategy boosts the efficacy of mRNA-based therapies, expanding the potential of mRNA vaccines and gene therapies.