Cysteine rich intestinal protein 2 links copper homeostasis to translational regulation in primary myoblasts

Copper (Cu) is an essential trace element for cellular metabolism, yet its roles in development are not fully defined. We identified murine cysteine-rich intestinal protein 2 (mCrip2) as a novel Cu-binding protein required for myoblast differentiation. RNA-seq of mCrip2 -deficient cells revealed downregulation of ribosome biogenesis and translation genes. Loss of mCrip2 reduced global protein synthesis by 20-30%, partially mimicking cycloheximide treatment. Interestingly, Cu supplementation restored protein synthesis despite persistent differentiation defects. These findings establish mCrip2 as a Cu-responsive regulator linking metal homeostasis to protein synthesis, suggesting a previously unrecognized connection between Cu availability and translational control in mammalian cells.