Pleckstrin homology domain-containing family N member 1 (PLEKHN1)

Pleckstrin homology domain-containing family N member 1 (PLEKHN1) is a phospholipid-binding protein characterized by the presence of pleckstrin homology (PH) domains, which facilitate interactions with various lipid species, including cardiolipin, phosphatidic acid, phosphatidylinositol 4-phosphate, and phosphatidylserine. PLEKHN1 localizes to the mitochondrial membrane and cytoskeleton and plays a key role in apoptosis, where it promotes Bax-Bak hetero-oligomerization via interaction with Bid, a pro-apoptotic Bcl-2 family member. Loss of PLEKHN1 protects cancer cells from apoptosis and is linked to resistance against hypoxia-induced cell death, implicating PLEKHN1 in tumor biology and drug resistance. It also participates in RNA biology by regulating stability of specific mRNAs (e.g., leptin mRNA) through interactions with the RNA stabilizer ELAVL1. PLEKHN1 interacts with proteins involved in the inflammatory response and can be found in vesicular compartments, nucleus, and mitochondria, suggesting diverse cellular functions. There are currently no known drugs directly targeting PLEKHN1, and its mechanism-of-action as a therapeutic target remains to be established.

Other names

Pleckstrin homology domain containing N1PH domain-containing family N member 1Cardiolipin and phosphatidic acid-binding proteinCLPABPDKFZP434H2010