AFG3L2 is a catalytic component of the mitochondrial m-AAA protease complex, a zinc metalloprotease with both ATPase and protease activities essential for mitochondrial proteostasis 1. The ATPase activity unfolds protein substrates for threading into the proteolytic cavity, where they are hydrolyzed into peptide fragments [UniProt]. AFG3L2 performs multiple critical functions: (1) quality control of inner mitochondrial membrane proteins by degrading mistranslated and misfolded polypeptides 2; (2) maturation of mitochondrial proteins including MRPL32, PINK1, and SPG7 through presequence cleavage [UniProt]; (3) regulation of mitochondrial calcium homeostasis by controlling SMDT1/EMRE availability for MCU assembly [UniProt]; (4) maintenance of glutathione homeostasis through iron-sulfur cluster-dependent degradation of the GSH transporter SLC25A39 34; and (5) regulation of OPA1 processing via OMA1 maturation [UniProt]. AFG3L2 also interacts with prohibitin 1 to regulate mitochondrial permeability transition pore opening and mtDNA release 5. Mutations in AFG3L2 cause dominant optic atrophy 12, spastic ataxia 5, and spinocerebellar ataxia 28 167, reflecting its essential roles in neuronal energy metabolism and axonal development.