Angiopoietin-like protein 2 (ANGPTL2)

Angiopoietin-like protein 2 (ANGPTL2) is a secreted glycoprotein of the angiopoietin-like family and shares structural similarity with classic angiopoietins, featuring an N-terminal coiled-coil domain and a C-terminal fibrinogen-like domain[1][2][3][4]. It is widely expressed in multiple tissues, including endothelium, adipose, muscle, and cells within organ niches[2][4][5]. ANGPTL2 mediates angiogenesis, inflammatory responses, lipid metabolism, tissue repair, and stem and progenitor cell regulation[1][2][3][4][5]. Its dysregulation is implicated in chronic inflammatory diseases (such as obesity, type 2 diabetes, atherosclerosis), cardiovascular disease, cancer (promoter of tumor cell migration, invasion, and metastasis; but also shows tumor-suppressive roles in certain contexts), and fibrotic disorders[4][5][6]. ANGPTL2 exerts its effects by autocrine and paracrine signaling, interacting with diverse receptors including LILRB2/PIRB (on hematopoietic stem cells), integrin α5β1 (on endothelial and stromal cells), and CD146 (on adipocytes and endothelial cells)[2][4]. It is not a classical receptor or enzyme but acts as a multifunctional secreted factor/cytokine that orchestrates tissue responses to injury, stress, and regeneration[1][4][5]. Elevated serum ANGPTL2 is considered a biomarker for chronic disease state severity and poor prognosis in multiple disease settings[4]. No drugs specifically targeting ANGPTL2 are clinically approved, but experimental approaches include monoclonal antibodies or RNA-based inhibitors in preclinical stages, and monitoring ANGPTL2 for patient stratification in trials[4][5][6]. Disruption of ANGPTL2 function can impair tissue and stem cell regeneration, while excess signaling fuels chronic inflammation and organ damage, indicating its biology is highly context- and cell-type dependent[5][6].

Other names

Angiopoietin-related protein 2ARP2HARPangiopoietin like 2angiopoietin-like protein 2UNQ170/PRO196

Inhibition/interference with ANGPTL2 blocks receptor binding (e.g., LILRB2/PIRB, integrin α5β1, CD146), potentially modulating angiogenesis, inflammation, tumor growth, stem cell function[2][4]