Pregnancy-associated plasma protease A2 (PAPPA2)

Pregnancy-associated plasma protease A2 (PAPPA2), also known as pappalysin-2, is a secreted zinc-metalloproteinase that plays a pivotal role in regulating the bioavailability of insulin-like growth factors (IGFs) (UniProt Q9BXP8) [1]. It specifically cleaves insulin-like growth factor binding protein-3 (IGFBP-3) and insulin-like growth factor binding protein-5 (IGFBP-5), which are the primary carriers of IGF-1 in the circulation (NCBI Gene 60676) [2]. By degrading these binding proteins, PAPPA2 releases free, bioactive IGF-1, allowing it to interact with the IGF-1 receptor and stimulate growth and metabolism (Overgaard et al., 2001) [3]. This proteolytic activity is essential for normal postnatal growth and skeletal development, as evidenced by human mutations leading to severe short stature characterized by high total IGF-1 but low free IGF-1 levels (Dauber et al., 2016) [4]. In clinical contexts, PAPPA2 is studied as a biomarker for pregnancy complications such as preeclampsia and fetal growth restriction, where its expression levels are often significantly altered (Conover and Oxvig, 2017) [5]. Although no small molecule inhibitors or recombinant PAPPA2 therapies are currently approved for clinical use, the protein remains a target of interest for treating growth disorders and managing certain cancers where IGF signaling is dysregulated.

Other names

Pappalysin-2PAPP-A2PL2Pregnancy-associated plasma protein A2

Cleavage of Insulin-like Growth Factor Binding Proteins (specifically IGFBP-3 and IGFBP-5), which releases bioactive IGF-1 to bind to its receptor and initiate signaling.