Abstract
Inositol polyphosphate-5-phosphatase E (INPP5E) is a 5-phosphatase critically involved in diverse physiological processes, including embryonic development, neurological function, immune regulation, hemopoietic cell dynamics, and macrophage proliferation, differentiation, and phagocytosis. Mutations in INPP5E cause Joubert and Meckel-Gruber syndromes in humans; these are characterized by brain malformations, microphthalmia, situs inversus, skeletal abnormalities, and polydactyly. Recent studies have demonstrated the key role of INPP5E in governing intracellular processes like endocytosis, exocytosis, vesicular trafficking, and membrane dynamics. Moreover, it regulates cellular signaling pathways by dephosphorylating the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate, phosphatidylinositol 4,5-bisphosphate, and phosphatidylinositol 3,5-bisphosphate. Despite recent advances, knowledge gaps persist regarding the function and molecular mechanism of INPP5E in various cells and species. This review integrates recent findings on the role of INPP5E in regulating cellular function, development, and the pathogenesis of various human disorders, emphasizing the molecular mechanism by which INPP5E regulates primary cilia assembly and function and critical signaling pathways. Identifying the importance of INPP5E in healthy and diseased states can advance our understanding of cellular processes and disease pathogenesis and provide a foundation for developing targeted therapeutic interventions.