Phosphatidylinositol-specific phospholipase C X domain containing 3 (PLCXD3)

Phosphatidylinositol-specific phospholipase C X domain containing 3 (PLCXD3) is a member of a subclass of phosphoinositide-specific phospholipase C (PI-PLC) enzymes that possess only the catalytic X domain and lack classical PH or C2 domains. It is highly expressed in human islets, rodent β-cells, and the brain, with lower levels in other tissues. PLCXD3 catalyzes phospholipid hydrolysis, generating inositol phosphates crucial for intracellular signaling. Its expression correlates positively with insulin and glucagon-like peptide 1 receptor (GLP1R) in pancreatic islets and is downregulated in diabetic states and with increased BMI. In functional studies, PLCXD3 depletion impairs glucose-stimulated insulin secretion, reduces β-cell insulin content, and downregulates key genes involved in insulin biosynthesis and glucose sensing, suggesting PLCXD3 as a regulator of β-cell function. Additional roles are reported in neuropsychiatric and neurodegenerative disorders, rapid-onset obesity (ROHHAD), and in spermatogenesis, where its expression serves as a biomarker in male infertility. There are currently no known drugs directly targeting PLCXD3, nor are there safety concerns documented for therapeutic targeting of this enzyme.

Other names

PI-PLC X domain-containing protein 3PLCXD3