MCL1 is an antiapoptotic BCL2 family member that regulates the balance between cell survival and apoptosis 1. The canonical isoform inhibits apoptosis by blocking BAX/BAK activation and preventing outer mitochondrial membrane permeabilization, while alternative splicing produces pro-apoptotic isoforms 1. Beyond apoptosis regulation, MCL1 functions as a metabolic hub: it modulates mTORC1 signaling to enhance mitochondrial oxidative phosphorylation and hexokinase-2 expression, promoting tumor bioenergetics 2. MCL1 is frequently overexpressed in hematologic and solid malignancies, where it drives chemotherapy resistance through cancer stem cell maintenance via mTORC1 activation and ROS generation 3. MCL1 also mediates drug resistance in cervical cancer by antagonizing apoptosis and promoting autophagy 4. Therapeutically, MCL1 inhibition triggers apoptosis through multiple mechanisms: BH3 mimetics block its prosurvival function 1, NOXA-mediated degradation reduces protein stability 5, and novel macrocyclic peptides induce homodimerization 6. Clinical utility is tempered by MCL1's physiological roles in non-hematologic tissues, causing cardiotoxicity with MCL1-targeting agents 2. Combined targeting of MCL1 with chemotherapy or PIM2 inhibitors shows enhanced efficacy in drug-resistant tumors 37.