From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease

Once a protein of relative obscurity, inositol polyphosphate multikinase (IPMK) emerged as a versatile and indispensable enzyme in cellular biology. With dual inositol and lipid kinase activities, IPMK generates pivotal signaling molecules such as InsP4 (inositol tetraphosphate), InsP5 (inositol pentaphosphate), and PIP3 (phosphoinositide 3,4,5-trisphosphate), positioning it as a critical regulator of cellular mechanisms. Initially identified in yeast and later recognized as essential for mammalian embryonic development, IPMK has transitioned from a niche interest to a focal point in studies of nutrient sensing, growth factor signaling, mRNA transport, and transcription regulation. Over two decades, multidisciplinary research has unveiled its far-reaching biological roles and implications in diverse diseases, including neurodegeneration, cancer, and inflammation. This review charts IPMK's journey from obscurity to prominence, examining its structure-function relationships, cellular roles, and emerging physiological impacts, while highlighting its potential as a therapeutic target in human health and disease.