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Genetic code expansion (GCE) technology offers an exciting alternative, enabling site\u2010specific incorporation of noncanonical amino acids (ncAAs) bearing uniquely reactive chemical groups into recombinant proteins expressed in diverse host cells. The resulting proteins can be chemoselectively labeled at the installed ncAA residues under mild conditions to generate homogeneous, site\u2010specific conjugates. In addition to offering site\u2010specificity, the small size of the ncAA residues minimizes the risk of structural perturbation, allowing access to many more internal sites in proteins relative to alternative site\u2010specific protein labeling approaches that require genetically encoded peptide and protein tags. Remarkable progress has been made in recent years, from improving the efficiency of ncAA incorporation at single or multiple sites, to expanding the palette of available chemistries, and applying this technology for both scientific discovery and the development of potential therapeutics and diagnostics. This review examines these advances and provides our perspectives on current challenges and future opportunities.<\/jats:p>","DOI":"10.1002\/anie.1922738","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T06:29:42Z","timestamp":1790317782000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Site\u2010Specific Protein Bioconjugation Through Cellular Incorporation of Noncanonical Amino Acids"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3700-6580","authenticated-orcid":false,"given":"Rahul","family":"Sarkar","sequence":"first","affiliation":[{"name":"Department of Chemistry Boston College  Chestnut Hill Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5989-776X","authenticated-orcid":false,"given":"Manas","family":"Joshi","sequence":"additional","affiliation":[{"name":"Department of Chemistry 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