FIS1 is a mitochondrial outer membrane protein that regulates mitochondrial fission, the division of the mitochondrial network into smaller units. FIS1 plays a minor role in recruiting dynamin-related protein 1 (DRP1) to mitochondria and facilitating membrane scission, though it may not be essential for assembly of functional fission complexes. FIS1 also mediates peroxisomal fission and can direct fission products toward mitophagy or apoptosis. FIS1 function is regulated by posttranslational modifications. Lactylation of FIS1 at lysine 20 promotes excessive mitochondrial fission, leading to ATP depletion and apoptosis 1, while deSUMOylation of FIS1 maintains mitochondrial integrity and endothelial function under hypoxic stress 2. FIS1 also recruits the TBC1D15 GTPase-activating protein to mitochondria-lysosome contacts to promote asymmetrical fission that selectively clears damaged mitochondria 3, a process protective against myocardial ischemia-reperfusion injury 4. Dysregulation of mitochondrial fission involving FIS1 has been implicated in multiple disease contexts. Reduced mitochondrial elongation via FIS1 deletion impairs metastatic progression in breast cancer 5. Genetic associations link FIS1 to ulcerative colitis risk via altered mitochondrial protein levels 6, and dysregulated mitochondrial dynamics involving FIS1 contribute to cardiac hypertrophy, heart failure, and sepsis-induced acute kidney injury 71. Targeting mitochondrial dynamics via FIS1 represents a potential therapeutic approach in multiple organ systems.