The panorama of GPLD1 in health and disease: Structural basis, metabolic remodeling, and new clinical horizons

GPLD1, an enzyme found in eukaryotes, plays a role in a variety of biological processes, including cell signaling, immune response, and metabolic regulation through specific hydrolysis of GPI-anchored proteins. This review systematically summarizes structural characteristics, catalytic mechanisms, and regulatory functions of GPLD1, emphasizing its crucial role in physiological regulation and disease pathogenesis, especially metabolic disorders, cancer, and neurodegenerative disease. Notably, GPLD1 has emerged as a key player in metabolic diseases, cancer, cardiovascular diseases and neurodegenerative disorders, where its expression is intricately regulated by factors such as diet, exercise, and chemical molecules. One striking aspect of GPLD1 is its tissue-specific, bidirectional regulation, influencing a variety of cellular pathways in a context-dependent manner. For instance, its regulation of insulin signaling pathways highlights its potential as a biomarker and therapeutic target in diabetes. Additionally, The multiple roles of GPLD1 in neurodegenerative diseases cancer and cardiovascular diseases indicate its broader relevance in disease progression and treatment. The review also discusses the potential of targeting GPLD1 pathways for drug development, offering new avenues for therapeutic intervention. Finally, the future of GPLD1 research points to the integration of advanced structural biology and personalized medicine approaches to better exploit its therapeutic potential.