Pleckstrin homology domain-containing family H member 2 (PLEKHH2)

Pleckstrin homology domain-containing family H member 2 (PLEKHH2) is a cytoplasmic scaffold protein characterized by tandem pleckstrin homology (PH) domains, a MyTH4 domain, and a FERM domain at the C-terminus[1][2][7]. It is expressed in tissues including the kidney glomerulus, where it may link podocyte foot processes to the glomerular basement membrane and stabilize F-actin by decreasing its depolymerization[2][7]. In cancer—especially non-small cell lung cancer—PLEKHH2 is often overexpressed, correlating with high tumor grade, increased proliferation, migration, and invasion, as well as poor prognosis[1]. Mechanistically, it binds β-arrestin1 via its FERM domain, thereby promoting focal adhesion kinase (FAK) phosphorylation and activating the PI3K/AKT signaling pathway, which stimulates cancer cell growth and invasion[1]. PLEKHH2 is a genetic risk locus for venous thromboembolism and is associated with certain rare tumors[2]. Currently, there are no known drugs targeting PLEKHH2 and no established mechanisms of drug action, but its strong association with tumor progression highlights its potential utility as a prognostic biomarker and a possible future therapeutic target[1][2][7].

Other names

KIAA2028PLEKHH1LPleckstrin homology, MyTH4 and FERM domain containing H2pleckstrin homology domain containing, family H (with MyTH4 domain) member 2