CMC1 is a mitochondrial intermembrane space protein containing a conserved twin CX9C motif that functions as a chaperone in cytochrome c oxidase (complex IV) assembly 1. CMC1 forms an early assembly intermediate with the COX1 subunit and assembly factors COA3 and COX14, stabilizing the COX1-COA3-COX14 complex before incorporation of later subunits 1. Unlike factors affecting COX1 metallation or late stability, CMC1 specifically regulates turnover of newly synthesized COX1 during maturation without altering COX1 synthesis rates 1. CMC1 functions cooperatively with its homologue CMC2, with each having nonoverlapping roles in complex IV biogenesis 2. Beyond mitochondrial function, CMC1 acts as an immunometabolic checkpoint in T cell immunity 3. CMC1 positively regulates CD8+ T cell activation and terminal differentiation, with elevated expression in exhausted T cells 3. CMC1 deletion impairs CD8+ T cell exhaustion development, promoting quiescent, memory-like cells with increased tolerance to death under repetitive TCR stimulation 3. Lactate in the tumor microenvironment enhances CMC1 expression through USP7-mediated stabilization, potentially linking metabolic conditions to T cell dysfunction 3. These findings suggest CMC1 represents a therapeutic target for improving anti-tumor immunity and treating complex IV deficiencies.