Phosphoinositide-3-kinase catalytic subunit delta (PI3Kδ)

Phosphoinositide-3-kinase catalytic subunit delta (PI3Kδ) is a class IA lipid kinase predominantly expressed in hematopoietic cells, including B and T lymphocytes, neutrophils, and mast cells (UniProt, 2024; Wikipedia, 2024). It plays a fundamental role in immune cell signaling by catalyzing the conversion of PIP2 to the second messenger PIP3, which recruits and activates downstream effectors like AKT to promote cell growth, survival, and differentiation (MedlinePlus, 2023; JensenLab, 2024). In B cells specifically, PI3Kδ is essential for B-cell receptor (BCR) signaling and homing to lymphoid tissues (Gilead Sciences, 2014). Dysregulation of PI3Kδ is a key driver in several diseases, most notably B-cell malignancies such as chronic lymphocytic leukemia (CLL) and follicular lymphoma, where hyperactive signaling promotes tumor cell survival (Patsnap Synapse, 2024). Furthermore, gain-of-function mutations in the PIK3CD gene lead to Activated PI3K Delta Syndrome (APDS), a rare primary immunodeficiency characterized by recurrent infections and lymphoproliferation (NIAID, 2024). Therapeutic strategies involve selective small-molecule inhibitors like idelalisib and leniolisib, which bind the ATP-binding pocket of the p110δ subunit to disrupt the oncogenic or overactive signaling cascade (BenchChem, 2025; ResearchGate, 2019).

Other names

PIK3CDp110δp110-deltaPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoformPtdIns-3-kinase subunit p110-deltaPhosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit deltaAPDSIMD14

Inhibition of the catalytic activity of the p110δ subunit, preventing the phosphorylation of phosphatidylinositol 4,5-bisphosphate (PIP2) to phosphatidylinositol 3,4,5-trisphosphate (PIP3), thereby blocking downstream AKT/mTOR signaling pathways.