PLCXD3 (phosphatidylinositol specific phospholipase C X domain containing 3) is a phospholipase involved in phosphoinositide signaling pathways with diverse tissue-specific functions. In pancreatic β-cells, PLCXD3 regulates glucose-stimulated insulin secretion and insulin content, with reduced expression correlating with impaired insulin signaling and downregulation of key genes including Insulin, NEUROD1, GLUT2, and GCK 1. The protein is highly expressed in human islets, and its expression inversely correlates with BMI and HbA1c levels in diabetic patients 1. Genetic variants in PLCXD3 (rs319013 and rs9292806) are associated with increased metabolic syndrome risk and altered glucose metabolism in healthy individuals 2. In reproductive biology, PLCXD3 is expressed in testicular germ cells and is regulated by miR-34c-3p, with protein absence observed in severe oligozoospermia patients 3. PLCXD3 also functions as a tumor suppressor in gastric cancer, where its downregulation promotes cell stemness, invasiveness, and EMT through Wnt/β-catenin pathway activation 4. Additionally, PLCXD3 variants have been investigated in neuropsychiatric disorders, with conflicting evidence regarding associations with bipolar disorder 5 and Creutzfeldt-Jakob disease 67. The protein appears to be primarily brain-expressed and involved in lipid catabolism and cellular signaling across multiple organ systems.