A synthetic biology group demonstrated simultaneous incorporation of five distinct noncanonical amino acids into a single protein in mammalian cells, significantly expanding the capability to program protein chemistry. The platform overcomes previous constraints on genetic code expansion and enables complex site‑specific modifications for therapeutic protein engineering. The technique integrates orthogonal tRNA/synthetase pairs and engineered codon reassignment strategies to place multiple ncAAs with high fidelity. Authors suggest immediate applications in designing multifunctional biologics, advanced imaging probes, and precision therapeutics. If scalable and manufacturable, this advancement could accelerate new modalities where bespoke chemistry on protein scaffolds delivers novel mechanisms of action or improved pharmacology.