PIP5K1C is a phosphatidylinositol kinase that catalyzes conversion of phosphatidylinositol 4-phosphate to phosphatidylinositol 4,5-bisphosphate (PIP2), a critical lipid second messenger regulating signal transduction, vesicle trafficking, actin cytoskeleton dynamics, cell adhesion, and cell motility. PIP2 serves as a precursor for other second messengers including inositol 1,4,5-trisphosphate and phosphatidylinositol 3,4,5-trisphosphate. PIP5K1C is required for clathrin-mediated endocytosis and synaptic vesicle transport, controls the plasma membrane PIP2 pool involved in synaptic exocytosis and endocytosis, and facilitates focal adhesion assembly by regulating talin targeting and integrin interactions. It also negatively regulates T-cell activation and adhesion. Loss of PIP5K1C in osteocytes causes reduced bone mass and impaired biomechanical properties 1, while deletion in chondrocytes results in spontaneous osteoarthritic lesions in aged mice 2. Biallelic pathogenic variants in PIP5K1C cause lethal congenital contractural syndrome 3, characterized by severe multiple joint contractures, muscle atrophy, and early respiratory failure 3. PIP5K1C deficiency in certain cancer cells increases sensitivity to PIKFYVE inhibitors, suggesting potential therapeutic applications 4. Recent evidence indicates PIP5K1C inhibition may contribute to antiviral mechanisms against SARS-CoV-2 5.