Eif3f, the f subunit of eukaryotic initiation factor 3, is crucial for mRNA translation initiation as part of the eIF3 complex. It is involved in multiple biological processes, with its dysregulation linked to various diseases [2,3,5].

In skeletal muscle, eIF3f overexpression leads to hypertrophy via the mTORC1 pathway, and it is a target of the E3 ubiquitin ligase MAFbx/atrogin-1 during atrophy [2]. Gene knockout studies in mice showed that homozygous eIF3f null mutants fail to develop and die at an early embryonic stage, while heterozygous mice with partial eIF3f depletion have reduced muscle mass due to decreased protein synthesis rate and MTORC1 pathway inhibition. During hindlimb immobilization, these heterozygous mice display exacerbated muscle atrophy [4].

In colorectal cancer, eIF3f is upregulated, and it enhances the Serine-Glycine-One-Carbon (SGOC) pathway by increasing the expression of phosphoglycerate dehydrogenase (PHGDH) through its deubiquitinating activity [1]. In hepatocellular carcinoma, eIF3f is also upregulated, promoting fatty acid biosynthesis and tumour malignancy by stabilizing long chain acyl CoA synthetase 4 (ACSL4) [3].

In conclusion, eIF3f is essential for embryonic development and muscle homeostasis through regulating protein synthesis. Its dysregulation in cancer, like colorectal and hepatocellular carcinoma, highlights its potential as a therapeutic target. The use of gene knockout mouse models has been instrumental in uncovering these functions and disease associations of eIF3f.