The Peptidyl-tRNA Hydrolase 2 (PTRH2) gene codes for a highly conserved mitochondrial protein. This protein prevents the accumulation of dissociated peptidyl-tRNA, and plays an important role in regulating cell survival and death. It promotes cell survival as part of an integrin-signaling pathway for cells attached to the extracellular matrix (ECM), through interaction with focal adhesion kinase (FAK) and subsequent activation of the PI3K-AKT-NFkB pathway. It also induces Bcl-2 transcription that blocks the intrinsic mitochondrial apoptotic pathway. PTRH2 functions as a phosphoprotein that regulates NFkB and ERK signaling. In cells that have lost their attachment to the ECM through anoikos, PTRH2 promotes apoptosis. Upon loss of integrin-mediated cell attachment to the ECM, PTRH2 protein is phosphorylated, is released from the mitochondria into the cytosol, and promotes apoptosis through interactions with transcriptional regulator amino-terminal enhancer of split (AES).
Defects in this protein have been associated with Infantile Multisystem Neurologic, Endocrine, and Pancreatic disease (INMEPD)., a progressive multisystem disease characterized by intellectual disability, progressive cerebellar atrophy, postnatal microcephaly, failure to thrive, hearing impairment, polyneuropathy, and organ fibrosis with exocrine pancreas insufficiency.