Displays phosphatase activity for serine/threonine residues, and, dephosphorylates and activates MAP3K5 kinase. Has apparently no phosphoglycerate mutase activity. May be regulator of mitochondrial dynamics. Substrate for a KEAP1-dependent ubiquitin ligase complex. Contributes to the repression of NFE2L2-dependent gene expression (By similarity). Acts as a central mediator for programmed necrosis induced by TNF, by reactive oxygen species and by calcium ionophore. H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] + phosphate H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] + phosphate Dimer. Forms a ternary complex with NFE2L2 and KEAP1. Interacts with BCL2L1 and MAP3K5 (By similarity). Upon TNF-induced necrosis, forms in complex with RIPK1, RIPK3 and MLKL; the formation of this complex leads to PGAM5 phosphorylation (By similarity). Interacts with DNM1L; this interaction leads to DNM1L dephosphorylation and activation and eventually to mitochondria fragmentation (By similarity). The N-terminal 35 amino acids, including the potential transmembrane alpha-helix, function as a non-cleaved mitochondrial targeting sequence that targets the protein to the cytosolic side of the outer mitochondrial membrane. Phosphorylated by the RIPK1/RIPK3 complex under necrotic conditions. This phosphorylation increases PGAM5 phosphatase activity (By similarity). Belongs to the phosphoglycerate mutase family. BPG-dependent PGAM subfamily.