Pleckstrin homology domain-containing family A member 5 (PLEKHA5)

Pleckstrin homology domain-containing family A member 5 (PLEKHA5) is a cytosolic adaptor protein involved in binding phosphatidylinositol phosphates and modulating intracellular signal transduction. It is expressed in multiple tissues and acts downstream of receptor tyrosine kinases such as Met, where it is subjected to regulated tyrosine phosphorylation. In cancer, especially diffuse-type gastric carcinoma with Met gene amplification, PLEKHA5 supports cell survival, resistance to apoptosis, and the maintenance of malignant phenotypes, including peritoneal dissemination. Its knockdown leads to apoptotic cell death in Met-addicted carcinoma cells and disrupts glycolytic metabolism, highlighting its functional importance in oncogenic signaling. Beyond its role in cancer, PLEKHA5 is predicted to be involved in reproductive system development and is associated with congenital syndromes such as cleft lip/palate and Temtamy syndrome. No drugs currently target PLEKHA5 directly, but its status as a critical effector downstream of Met makes it a candidate for future therapeutic intervention.

Other names

Pleckstrin homology domain containing A5KIAA1686PEPP2PH domain-containing family A member 5FLJ10667Phosphoinositol 3-phosphate-binding protein 2pleckstrin homology domain-containing family A member 5phosphoinositol 3-phosphate-binding protein-2

No drugs directly targeting PLEKHA5 are currently described; however, its function is linked to Met signaling and it is tyrosine-phosphorylated downstream of Met. Drugs inhibiting Met reduce PLEKHA5 phosphorylation and dependent signaling.