Strategies to Mitigate Allergenicity of Edible Insect Proteins: Mechanisms, Synergistic Approaches, and Future Directions for Low‐Allergenicity Insect Food Development

Edible insects have emerged as a sustainable alternative protein source, yet their widespread application in food systems is constrained by well-established allergenic risks. Accumulating evidence indicates that insect proteins cannot be assumed to be inherently low-allergenic, largely due to the presence of highly conserved pan-allergens sharing significant sequence homology and extensive cross-reactivity with crustaceans and mites. This review provides a comprehensive and mechanism-oriented overview of the physicochemical characteristics, immunological determinants, and processing-induced structural alterations of major insect allergens, with a particular focus on tropomyosin, arginine kinase, and other clinically relevant allergenic proteins. We critically examine how protein stability, epitope distribution, and digestion resistance govern IgE-binding capacity and cross-reactive immune responses. Current allergenicity mitigation strategies, including enzymatic hydrolysis, thermal processing, non-thermal physical technologies, and chemical or structural modifications, are systematically discussed with respect to their efficacy, limitations, and impacts on nutritional and sensory quality. Particular emphasis is placed on emerging synergistic approaches that integrate structural destabilization with targeted enzymolysis to achieve more effective allergenicity reduction. Finally, future perspectives are proposed, highlighting the need for precision regulation of allergenic proteins at the epitope and structural-domain levels, standardized allergenicity assessment frameworks, and improved translational relevance between in vitro assays and clinical outcomes. By integrating molecular mechanisms with food processing strategies, this review aims to provide a scientific basis for the development of safer, nutritionally adequate, and consumer-acceptable insect-based foods.