MTCH2 (mitochondrial carrier 2) is a multifunctional protein insertase located on the mitochondrial outer membrane that plays critical roles in cellular metabolism, apoptosis, and energy homeostasis. As a protein insertase, MTCH2 mediates insertion of α-helical transmembrane proteins including signal-anchored, tail-anchored, and multi-pass membrane proteins into the mitochondrial outer membrane, but not β-barrel proteins 1. The protein functions as a gatekeeper controlling protein mislocalization and modulating apoptotic sensitivity in leukemia cells 1. MTCH2 serves as a negative regulator of thermogenesis and energy expenditure, with adipose-specific depletion protecting against diet-induced obesity by promoting brown adipose tissue thermogenesis and white adipose tissue browning 2. The protein suppresses thermogenesis through negative regulation of autophagy via Bcl-2-dependent mechanisms 2. MTCH2 deletion creates a high ATP demand environment that prevents adipocyte differentiation by failing to support the anabolic processes required for lipid accumulation 3. In disease contexts, MTCH2 expression is significantly increased in obese individuals and enriched in adipocytes 4. Additionally, MTCH2 regulates ferroptosis in colorectal cancer through the E2F4/TFRC pathway, with deficiency sensitizing tumors to sorafenib treatment 5.