Dcaf12, short for Damaged DNA-binding protein-1 (DDB1)- and CUL4-associated factor 12, is a crucial protein. It functions as the substrate recognition component within the Cullin4-RING E3 ligase (CRL4) complex, identifying C-terminal double-glutamic acid degrons to regulate protein degradation through the ubiquitin proteasome system. It is involved in multiple biological pathways, such as apoptosis regulation and NF-κB activation, and is of great biological importance in processes like spermatogenesis, T -cell activation, and synaptic function [1,2,3]. Drosophila and mouse models have been valuable in studying its functions.

In mice, Dcaf12 knockout leads to fewer mature sperms in testes, along with elevated MOV10 and an imbalance in meiotic markers SCP3 and γ-H2AX, demonstrating its role in spermatogenesis. Activated Dcaf12 -deficient T cells show inappropriately stabilized MOV10 and increased levels of activated caspases, indicating its significance in T -cell activation [2]. In Drosophila, deletion of Dcaf12 impairs larval locomotion, arrests development, and affects neurotransmitter release, synaptic receptor levels, and homeostatic plasticity at larval neuromuscular junctions [3].

In summary, Dcaf12 is essential for various biological processes including spermatogenesis, T -cell activation, and synaptic function. Gene knockout models in mice and Drosophila have been instrumental in revealing its role in these processes, potentially providing insights into related human diseases such as male infertility and immune-related disorders.