Dcaf12, also known as Damaged DNA-binding protein-1 (DDB1)- and CUL4-associated factor 12, is a key component within the Cullin4-RING E3 ligase (CRL4) complex. It functions as a substrate recognition molecule, identifying C-terminal double-glutamic acid degrons to facilitate the degradation of specific substrates via the ubiquitin-proteasome system. It is involved in multiple biological pathways such as apoptosis regulation, NF-κB activation, spermatogenesis, T-cell activation, and synaptic function [1,2,3,4].

In a Dcaf12 knockout mouse model, it was demonstrated that DCAF12-mediated degradation of MOV10, an "ancient" RNA-induced silencing complex (RISC) complex RNA helicase, is conserved in mice and humans. Dcaf12-deficient mice had testes that produced fewer mature sperms, with elevated MOV10 and an imbalance in meiotic markers SCP3 and γ-H2AX. Also, the percentages of splenic CD4+ T and natural killer T (NKT) cell populations were significantly altered. In vitro, activated Dcaf12-deficient T cells showed inappropriately stabilized MOV10 and increased levels of activated caspases, revealing the role of Dcaf12 in spermatogenesis and T-cell activation [3].

In conclusion, Dcaf12 is crucial for various biological functions including apoptosis, NF-κB activation, spermatogenesis, and T-cell activation. The Dcaf12 knockout mouse model has been instrumental in uncovering its role in spermatogenesis and T-cell-related processes, providing insights into potential mechanisms underlying related diseases.