CUL4A regulates numerous key processes such as DNA repair, chromatin remodeling, spermatogenesis, haematopoiesis and the mitotic cell cycle.

This modification appears to induce conformational changes which promotes flexibility in the RING domain of cullin proteins and enhanced ubiquitin ligase activity.

[12][13] The yeast homolog of CUL4A, Rtt101, ubiquitinates histone H3 and promotes nucleosome assembly and CRL4A complexes perform similar functions in human cells.

[23] CRL4A complexes appear to induce the degradation of numerous members of the HOX transcription family, which are essential regulators of haematopoiesis.

[24] The first member of the HOX family identified as a target of CRL4A-mediated degradation is HOXA9, which is essential for haematopoietic stem cell maintenance and has been implicated in a subset of myeloid leukemias.

It is at these stages that CUL4A-deficient male germ cells exhibit high levels of apoptosis, improper DNA repair and accumulation of the CRL4 substrate Cdt1.

The chromosomal region ch13q34 which contains the CUL4A gene is amplified in 3-6% of certain carcinomas including: breast, uterine, lung, stomach and colorectal cancers.

[30] Due to the observed amplification of CUL4A in several carcinomas and the fact that CRL4 complexes target multiple DNA repair and tumor suppressor genes, CUL4A can be considered an oncogene in certain contexts.

Due to its robust expression (particularly during DNA replication) and modular nature, CRL4A complexes can be co-opted or "hijacked" to promote viral proliferation in mammalian cells.

Although DCAF1/VPRBP appears to have a crucial function in tumor suppression, DNA replication and embryonic development, HIV-1 "hijacks" the ubiquitin ligase complex to induce arrest of the cell cycle in G2 phase.

[40] Thalidomide and other derivatives such as pomalidomide and lenalidomide are known as immunomodulatory drugs (or IMiDs) and have been investigated as therapeutic agents for autoimmune diseases and several cancers - particularly myelomas.

Recent reports show that IMiDs bind to CRL4CRBN and promote the degradation of IKZF1 and IKZF3 transcription factors, which are not normally targeted by CRL4 complexes.