Presenilin-associated rhomboid-like protein, mitochondrial (PARL)

Presenilin-associated rhomboid-like protein, mitochondrial (PARL), is an **inner mitochondrial membrane serine protease** belonging to the rhomboid protease family[1]. It regulates mitochondrial remodeling, integrity, and apoptosis by cleaving various membrane-anchored mitochondrial proteins, including PINK1, PGAM5, and OPA1[1][4]. Through these functions, PARL modulates processes such as **mitophagy**—the selective degradation of damaged mitochondria—cell survival, and apoptotic signaling[5][3]. Dysfunction or genetic variants of PARL have been associated with increased risk of neurodegenerative conditions (such as **Parkinson’s disease**), **type 2 diabetes**, and mitochondrial-related optic neuropathies[1][4]. Chemical inhibitors of PARL have been developed as research tools to study its role in mitophagy and disease contexts, but are not currently used therapeutically[3]. Potential safety concerns for PARL inhibition include the possibility of impairing mitochondrial function and cell survival through disrupted regulation of apoptosis and protein quality control[1][3][4].

Other names

PINK1/PGAM5-associated rhomboid-like proteasePSARLPresenilins-associated rhomboid-like proteinPARL_HUMAN

Inhibition of intramembrane proteolysis of substrates such as PINK1 and PGAM5, leading to modulation of mitophagy[3]