PIK3CB encodes the catalytic β-subunit of phosphatidylinositol 3-kinase (PI3K), a key signaling enzyme that phosphorylates phosphatidylinositol 4,5-bisphosphate to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3), recruiting and activating AKT and other PH domain-containing proteins to control cell growth, survival, proliferation, and motility. PIK3CB functions downstream of receptor tyrosine kinases and G-protein-coupled receptors, and is required for platelet adhesion and aggregation. Beyond its canonical lipid kinase role, PIK3CB exhibits kinase-independent scaffolding functions in autophagy, insulin signaling, and clathrin-mediated endocytosis. PIK3CB is frequently dysregulated in human cancers. Rare oncogenic PIK3CB mutations display gain-of-function activity and transform cells in vitro 1. In castration-resistant prostate cancer, copy-number gains of PIK3CB enriched at progression on taxane therapy are associated with chemotherapy resistance 2. In ovarian cancer, hnRNPL phase separation activates PIK3CB transcription and glycolysis to promote tumorigenesis 3. In gastric cancer, transcription factor SP1 upregulates PIK3CB expression to activate AKT signaling and drive proliferation and migration 4. Loss of KLHL21 in gastric cancer enhances PIK3CB translation, activating STAT3 and promoting metaplasia-to-cancer transition 5. Additionally, lactylation of PIK3CB rewires its activity to suppress antitumor immunity 6. Multiple PI3K inhibitors targeting PIK3CB—including buparlisib, pictilisib, alpelisib analogs, and TGX-221—show therapeutic potential in preclinical and clinical settings, with TGX-221 demonstrating activity against gastric cancer cells 4.