Eftud2, also known as elongation factor Tu GTP binding domain containing 2, is a spliceosomal GTPase and an essential constituent of U5 small nuclear ribonucleoproteins (snRNPs). It plays a crucial role in spliceosome activation, which is essential for the removal of introns from precursor mRNA, thus regulating embryonic development and innate immunity [3].

In a conditional knockout (CKO) mouse model where Eftud2 was specifically ablated in cerebellar Purkinje cells, severe ferroptosis, Purkinje cell degeneration, dyskinesia, and cerebellar atrophy occurred, recapitulating phenotypes seen in patients with mandibulofacial dysostosis with microcephaly (MFDM) syndrome. Mechanistically, Eftud2 promotes Scd1 and Gch1 expression, upregulates monounsaturated fatty acid phospholipids, and enhances antioxidant activity to suppress Purkinje cell ferroptosis. Also, transcription factor Atf4 was identified as a downstream target regulating anti-ferroptosis effects in a p53 - independent manner [1].

In another CKO mouse model (CX3CR1 - CreER; Eftud2f/f cKO) for microglia - specific Eftud2 deficiency, abnormal proliferation and an anti - inflammatory phenotype activation of microglia were observed, suggesting Eftud2 plays a key role in regulating microglial polarization and homeostasis possibly through the NF - κB signaling pathway [2].

In conclusion, Eftud2 is essential for maintaining normal biological functions. Its deficiency in specific cell types in KO/CKO mouse models reveals its role in preventing ferroptosis - related neurodegeneration and regulating microglial activation. These findings contribute to understanding diseases such as MFDM syndrome and potentially neurodegenerative diseases related to microglial dysregulation [1,2].