Phosphoglycerate mutase 5 (PGAM5)

Phosphoglycerate mutase 5 (PGAM5) is a mitochondrial membrane–anchored enzyme classified as an atypical serine/threonine phosphatase, belonging to the histidine phosphatase superfamily[1][4]. Unlike other phosphoglycerate mutase family members, PGAM5 does not catalyze the conversion of 3-phosphoglycerate to 2-phosphoglycerate in glycolysis, despite its structural similarity; rather, it displays phosphatase activity toward protein substrates and plays major roles in mitochondrial quality control, regulation of oxidative stress, and several regulated cell death pathways, such as apoptosis and necroptosis[2][3][4]. Its regulation involves oligomerization and allosteric activation by N-terminal motifs, and it interacts with mitochondrial proteins to modulate processes such as mitophagy, fission/fusion, and cellular responses to stress[1][4]. PGAM5 is implicated in multiple disease contexts including cancer, cardiovascular disease, and neurodegeneration, making it a potential therapeutic target for future drug development[4][2].

Other names

PGAM family member 5PGAM-5mitochondrial phosphatase PGAM5

Drugs targeting PGAM5 would theoretically act as: Phosphatase inhibitors or activators (modulating the dephosphorylation of protein substrates); Modulators of mitochondrial quality control and cell death signaling.