Lethal giant larvae protein homolog 2 (LLGL2)

Lethal giant larvae protein homolog 2 (LLGL2) is a highly conserved, non-enzymatic scaffolding protein that functions primarily in the regulation of apical-basal cell polarity, organization of cell junctions, and control of cell proliferation in epithelial tissues. LLGL2 is a core component of the Scribble polarity complex, along with Scribble (SCRIB) and Discs large (DLG), which antagonizes other polarity modules (such as Par and Crumbs complexes) to establish and maintain epithelial organization and tissue architecture. Structurally, LLGL2 contains a double β-propeller domain, and its association with the plasma membrane is regulated by phosphorylation via atypical protein kinase C (aPKC); this phosphorylation serves as a switch controlling its membrane localization and function[1][2][5]. Functionally, LLGL2 acts as a dynamic scaffold, regulating protein-protein interactions necessary for adherens and tight junction formation and maintenance, as well as maintaining epithelial barrier function and branching morphogenesis, such as in placental development[7]. As a tumor suppressor, the loss or dysfunction of LLGL2 is associated with disruption of cell polarity, increased ectopic proliferation, and promotion of tumorigenesis in various contexts[2][3][4]. Currently, LLGL2 is not a direct therapeutic target or known drug receptor, but its biological role as a tumor suppressor and regulator of epithelial integrity implicates it in diseases such as cancer and developmental defects when mutated or dysregulated[2][3][4][7].

Other names

HGLHugl-2LGL2Human giant larvae homolog 2Lethal(2) giant larvae protein homolog 2Scribble cell polarity complex component 2