AFG1L (AFG1 like ATPase) is a mitochondrial integral membrane protein that functions as an AAA-ATPase with critical roles in mitochondrial protein quality control and apoptosis. Structurally, AFG1L exists as part of multi-subunit complexes (~140-500 kDa) and requires an intact ATPase domain for its catalytic activities 1. Functionally, AFG1L mediates degradation of excess nuclear-encoded respiratory complex IV subunits (COX4I1, COX5A, COX6A1) and is essential for maintaining normal activity of complexes III and IV 1. Beyond protein degradation, AFG1L promotes mitochondrial morphology organization, maintaining fused mitochondrial reticulum and lamellar cristae structure 1. AFG1L also mediates transcription-independent apoptosis by facilitating p53 translocation into mitochondria in response to genotoxic stress 2. Disease relevance includes associations with breast cancer prognosis, where higher AFG1L expression correlates with poorer outcomes in a mitochondria-related prognostic model 3. Additionally, AFG1L has been identified as a candidate gene in atopic dermatitis and psoriasis 4, and copy number variations in AFG1L are associated with dementia risk 5. These findings establish AFG1L as a multifunctional mitochondrial protein linking bioenergetic homeostasis to cell death regulation.