Leucine-rich repeat-containing protein 32 (GARP) (GARP)

Leucine-rich repeat-containing protein 32 (LRRC32), also known as GARP, is a type I transmembrane protein with 20 leucine-rich repeats in its extracellular domain that serves as a key regulator of transforming growth factor beta (TGF-β) bioavailability and activation. It anchors latent TGF-β (particularly TGF-β1) to the cell surface via disulfide bonds with the latency-associated peptide (LAP), enabling integrin-dependent activation on cells like activated regulatory T cells (Tregs), platelets, and megakaryocytes. This function is critical for immune suppression by Tregs, tissue remodeling, and developmental processes such as palate fusion via TGF-β3 regulation. LRRC32 expression is upregulated on activated FOXP3+ Tregs, where it tethers latent TGF-β to facilitate targeted delivery at immune response sites. Dysregulation links it to pathologies including cancer (via tumor-induced Treg suppression), fibrosis, autoimmunity, and developmental disorders like cleft palate with proliferative retinopathy. As a therapeutic target, anti-GARP antibodies like livmoniplimab (ABBV-151) are in development to block surface TGF-β on Tregs, potentially treating cancer and chronic infections with reduced autoimmune risks compared to other checkpoint inhibitors.

Other names

LRC32glycoprotein A repetitions predominant

Anti-GARP monoclonal antibody inhibiting Treg function and TGF-beta activation on cell surface