DCAF4 (DDB1 and CUL4 associated factor 4) functions as a substrate receptor for CUL4-DDB1 E3 ubiquitin ligase complexes, playing critical roles in protein degradation and cellular regulation 1. The protein forms CRL4DCAF4 E3 ligase complexes with CUL4A/4B and DDB1, which specifically direct the ubiquitination and degradation of tumor suppressor ST7 in colorectal cancer 12. DCAF4 also mediates ubiquitination of optineurin (OPTN) and facilitates autophagic degradation of misfolded SOD1 proteins, suggesting a role in protein quality control relevant to amyotrophic lateral sclerosis 3. Expression of DCAF4 is regulated by c-Myc through binding to conserved promoter sequences and is overexpressed in various cancers including lung adenocarcinoma and colorectal cancer 14. Genetic variants in DCAF4 are associated with multiple phenotypes: rs2535913 affects leucocyte telomere length through regulation of DCAF4 expression 5, while rs12587742 increases lung cancer risk by upregulating DCAF4 mRNA expression and decreasing methylation 6. DCAF4 is also implicated in irinotecan resistance in colorectal cancer and keloid formation in African Americans 78.