Phosphoglycerate mutase family member 5 (PGAM5)

Phosphoglycerate mutase family member 5 (PGAM5) is a mitochondrial membrane-associated serine/threonine protein phosphatase that acts as an atypical member of the phosphoglycerate mutase family, lacking classical isomerase activity[1][3]. It regulates mitochondrial dynamics, cell death (including apoptosis and necroptosis), mitophagy, metabolism, and oxidative stress responses[1][2][3][4]. PGAM5 mediates its effects by dephosphorylating substrates such as BCL-xL and FUNDC1 in a stress-dependent manner, governing the molecular switch between cell survival and programmed cell death[2][4]. Its activity is modulated through oligomerization, forming dodecamers essential for catalytic function and mitochondrial membrane organization[1][3]. Genetic ablation or dysregulation of PGAM5 is associated with neurodegeneration, inflammation, cancer, and other mitochondria-related diseases[3][4]. While PGAM5 represents a promising research target for therapeutics aimed at modulating cell death and mitochondrial health, there are no approved direct pharmacological inhibitors or activators as of 2024[2][5].

Other names

Serine/threonine-protein phosphatase PGAM5, mitochondrialMGC5352BXLBv68Bcl-XL-binding protein v68Phosphoglycerate mutase family member 5BXLBV68serine/threonine-protein phosphatase PGAM5, mitochondrialPGAM family member 5, serine/threonine protein phosphatase, mitochondrialphosphoglycerate mutase family member 5

Dephosphorylation of protein substrates (e.g., BCL-xL, FUNDC1, BAX, DRP1, CypD) involved in regulation of cell death, mitophagy, and mitochondrial function[2][4]; Targeting of PGAM5 for therapeutic modulation could involve allosteric inhibition/activation or disruption of substrate interactions