INPP5A encodes an inositol polyphosphate-5-phosphatase that hydrolyzes inositol 1,4,5-trisphosphate to inositol 1,4-bisphosphate and inositol 1,3,4,5-tetrasphosphate to inositol 1,3,4-trisphosphate, thereby terminating IP3-mediated intracellular calcium signaling. The enzyme is membrane-associated and farnesylated, with reversible palmitoylation regulating its subcellular localization and function. INPP5A is expressed in the central nervous system and plays a role in dendritic spine morphogenesis. A microduplication in INPP5A segregates with schizophrenia spectrum disorder and autism spectrum disorder, suggesting altered calcium signaling contributes to early-onset psychiatric disease 1. In cancer, INPP5A acts predominantly as a tumor suppressor. In uveal melanomas driven by GNAQ/GNA11 mutations, INPP5A is required to prevent calcium overload and apoptosis by regulating IP3-evoked calcium oscillations 2; however, this dependency also identifies INPP5A as a synthetic lethal target 3. In cutaneous squamous cell carcinoma, low INPP5A expression predicts aggressive tumors and worse survival 4. Similarly, in esophageal squamous cell carcinoma and pituitary neuroendocrine tumors, INPP5A downregulation promotes malignant progression through PI3K/Akt pathway activation 5, 6. INPP5A expression correlates with improved outcomes across multiple cancer types. Recent evidence also links INPP5A to cognitive function and post-exercise muscle memory 7, 8.