INPP5A (inositol polyphosphate-5-phosphatase A) is a membrane-bound phosphatase that hydrolyzes inositol 1,4,5-trisphosphate (IP3) to inositol 1,4-bisphosphate and inositol 1,3,4,5-tetrasphosphate to inositol 1,3,4-trisphosphate 123. This catalytic activity regulates calcium signaling by controlling IP3-mediated intracellular calcium release. INPP5A is reversibly palmitoylated and farnesylated, targeting it to subcellular compartments where it modulates calcium oscillation frequency 4. The enzyme functions as a tumor suppressor across multiple cancer types. In GNAQ/GNA11-mutant uveal melanomas, INPP5A suppression causes IP3 accumulation, hyperactivating IP3-receptor signaling and triggering p53-dependent apoptosis, making it a synthetic lethal vulnerability 54. In esophageal squamous cell carcinoma and cutaneous squamous cell carcinoma, INPP5A downregulation correlates with poor prognosis, increased invasiveness, and metastasis 67. In pituitary neuroendocrine tumors, INPP5A acts as a tumor suppressor by negatively regulating PI3K/Akt signaling through IP3 degradation, with transcriptional repression mediated by PKA/MBD2 signaling 8. Additionally, INPP5A exhibits an epigenetic memory of high-intensity interval training in skeletal muscle, with retained hypomethylation correlating with enhanced expression 9, and blood-based INPP5A methylation associates with phonemic verbal fluency 10.