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This review critically examines two complementary paradigms, specialty milk utilization and synthetic biology\u2010enabled precision manufacturing, as transformative strategies for developing biomimetic IF ingredients. Specialty milks, including goat milk, camel milk, donkey milk, buffalo milk, and yak milk, exhibit compositional proximity to BM in specific dimensions, including digestibility, sn\u20102 fatty acid profiles, and fat globule size distribution. Synthetic biology platforms have achieved notable industrial\u2010scale successes, particularly in producing 2\u2032\u2010fucosyllactose and recombinant lactoferrin. However, significant knowledge gaps persist: the reconstruction of complex multi\u2010site phosphorylation, the high\u2010fidelity assembly of triple\u2010layer milk fat globule membranes, and cost\u2010effective large\u2010scale production remain unresolved challenges. Critically, most studies focus on single components rather than integrated formula systems, and robust clinical validation is lacking. This review argues that the convergence of specialty milk matrices with precision\u2010fermented bioactives represents a paradigm shift from compositional to structure\u2010function biomimicry. Priority research areas include multi\u2010omics\u2010based integration strategies, harmonized regulatory frameworks, and well\u2010designed clinical trials to establish functional equivalence. Addressing these gaps will be essential for developing next\u2010generation IF that more closely emulates the functional complexity of BM.<\/jats:p>","DOI":"10.1111\/1541-4337.70572","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T05:32:39Z","timestamp":1785130359000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Special Milk and Synthetic Biology: A Dual\u2010Perspective Review of Ingredient Substitutions in Breast\u2010Milk\u2010Simulated Infant Formula"],"prefix":"10.1111","volume":"25","author":[{"given":"Chao","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Food Science and Resource Nanchang University  Nanchang China"},{"name":"School of Food Science and Technology Nanchang University  Nanchang China"},{"name":"Jiangxi Province Key Laboratory of Food Allergy  Nanchang 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