MFF (mitochondrial fission factor) is a critical regulator of mitochondrial and peroxisomal division that functions as an adaptor protein facilitating DRP1 (dynamin-related protein 1) recruitment to mitochondrial membranes 1. MFF specifically governs midzone mitochondrial fission, a process distinct from peripheral fission, where ER-mediated pre-constriction and actin dynamics initiate division before MFF-dependent DRP1 recruitment drives scission 1. MFF coordinates with other fission machinery including the ER and actin cytoskeleton to define mitochondrial division sites 2. The protein undergoes phosphorylation at Ser172/Ser146 residues to enhance its activity in recruiting DRP1 during fission 3. MFF also participates in mitochondrial-derived vesicle (MDV) biogenesis through MID49/MID51-dependent mechanisms that facilitate DRP1-mediated scission 4. Beyond fission, MFF interacts with CerS6-derived sphingolipids, linking lipid metabolism to mitochondrial fragmentation in obesity 5. Dysregulation of MFF contributes to multiple diseases: excessive MFF-mediated fission accompanies dilated cardiomyopathy through aberrant RAS/RAF1/p44/42 kinase signaling 6, while impaired mitochondrial dynamics involving MFF dysregulation characterizes type 2 diabetes 7. MFF dysfunction is also associated with encephalopathy due to defective mitochondrial and peroxisomal fission. Therapeutic targeting of MFF-regulated fission represents a promising strategy for metabolic and cardiac diseases.