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Researches are being conducted to identify better stabilizing, low immunogenicity and highly active alternative sources has focused on marine microorganisms. Marine-derived L-asparaginase is a promising candidate due to its unique characteristics and broad application potential. This review discusses the molecular structure, production-related genes, and the search for marine microbial sources of L-asparaginase production. Roles of L-asparaginase in cancer metabolism including asparagine depletion, apoptosis induction, autophagy and immunity are also detailed. Clinical studies with L-asparaginase in the treatment of pediatric and adult acute lymphoblastic leukemia is described, with indications for solid\u00a0tumors. Also, combination therapy using L-asparaginase such as chemotherapy, targeted therapy, and immunotherapy has been explored to enhance therapeutic effects. 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