Structure and Roles of Phospholipase C (PLC), Phosphatidylinositol 4,5-bisphosphate (PIP2), and Inositol 1,4,5-trisphosphate (IP3) in Metabolism and Disease: A Systematic Review

Phospholipase C (PLC) enzymes are vital for various body functions as they facilitate key signaling pathways that regulate numerous physiological processes. PLC in eukaryotic cells converts phosphatidylinositol 4,5-bisphosphate (PIP 2 ) into inositol 1,4,5-triphosphate (IP 3 ), and diacylglycerol, a pivotal pathway modulating intracellular calcium levels. The systematic review investigates the structural characteristics and metabolic pathways of PLC, PIP 2 , and IP 3 within human systems, examining isoform functions of PLC and potential therapeutic applications. Specifically, different PLC subfamilies and isozymes across cells and tissues can alter the effect of the pathway through distinct PIP 2 binding affinities, enzyme expressions, activation modes, and activity rates. PIP 2 , an inner membrane component, participates in multiple signaling pathways—PLC, PI3K/AKT/mTOR, and phosphatidylinositol 5 phosphate—modulating diverse cellular functions. The secondary messenger IP 3 predominantly regulates intracellular Ca 2+ levels via IP 3 receptor-associated calcium ion channels. Alterations in this pathway, from PLC mutations to receptor variations and antagonist presence, can impact human cellular functions with diverse clinical implications. Therapeutic potential exists to modulate specific functions through the PLC-PIP 2 -IP 3 pathway, though certain PLC targets are challenging for drug development due to their critical roles and complex networks. Further research is necessary to comprehensively grasp the clinical implications and potential of targeting specific pathway components.