YME1L1 encodes an ATP-dependent metalloprotease localized to the mitochondrial inner membrane that plays critical roles in mitochondrial quality control and proteome regulation 1. The primary function involves degradation of folded and unfolded proteins with suitable degron sequences in the mitochondrial intermembrane space, particularly regulating mitochondrial morphology through OPA1 cleavage 2. YME1L1 maintains normal cristae morphology, complex I respiration activity, and protects against oxidatively damaged membrane proteins 3. The protease responds to cellular stress by mediating proteolytic rewiring of the mitochondrial proteome - during nutrient starvation, YME1L1 degrades translocases, lipid transfer proteins, and metabolic enzymes to limit mitochondrial biogenesis through an mTORC1-LIPIN1-YME1L1 signaling axis 4. YME1L1 also governs unoccupied protein translocase channels by eliminating TIM23 components when import is impaired 5. Disease relevance includes association with optic atrophy, 3-methylglutaconic aciduria with sensorineural hearing loss and neurological abnormalities 3, and acute kidney injury through SREBP1c-mediated transcriptional repression 6. Clinically, YME1L1 dysfunction results in compromised mitochondrial energy metabolism and enhanced mitochondrial fragmentation, while overexpression promotes cancer cell growth in non-small cell lung cancer 7.