Eif3d, the eukaryotic initiation factor 3 subunit D, is an RNA-binding subunit of the eIF3 complex with an RNA-binding motif and a cap-binding domain. It plays crucial roles in maintaining eIF3 complex integrity, global protein synthesis, and is involved in biological and pathological processes. It is known to regulate noncanonical cap-dependent translation of specific mRNAs, which contributes to processes like metabolic stress adaptation and disease onset and progression [2].

Cells respond to stress by reducing global protein synthesis and activating survival-related gene programs. During persistent stress, eIF3d activates the translation of the kinase GCN2, leading to eIF2α phosphorylation and inhibition of general protein synthesis. Concurrently, eIF3d upregulates the m6A demethylase ALKBH5, which drives 5' UTR-specific demethylation of stress response genes like ATF4. This ultimately converges on ATF4 expression, highlighting eIF3d's role as a critical effector in controlling core stress response orchestrators [1].

In cervical carcinoma, EIF3D promotes cell growth and the Warburg effect, and its inhibition may be a potential therapeutic strategy [3]. In colorectal cancer, EIF3D promotes resistance to 5-fluorouracil through upregulating RUVBL1 [4]. In breast cancer, the DAP5/eIF3d complex is essential for metastasis, EMT, and tumor-directed angiogenesis, carrying out selective translation of relevant mRNAs [5].

In conclusion, Eif3d is essential for various biological functions, especially in stress response and translation regulation. Model-based research, including studies on eIF3d in diseases such as cervical carcinoma, colorectal cancer, and breast cancer, has revealed its significant roles in tumor-related processes. Understanding Eif3d's functions may provide new insights into disease mechanisms and potential therapeutic targets.