Apoptosis, or regulated cell death, is a carefully controlled developmental process for multicellular organisms. Cells intentionally die when they are damaged or defunct. However, cancers characteristically evade apoptosis to divide and grow in an unrestrained manner. To do this, many cancers have mutated P53, a master regulator gene that is capable of initiating the apoptotic signalling pathway. Therefore, as many chemotherapies depend on P53 to kill cancer cells, bypassing the requirement for P53 in promoting apoptosis would be a powerful tool in our therapeutic arsenal. Our lab has conducted unbiased CRISPR/Cas9 whole genome screens to identify new regulators of the apoptotic process induced by P53. By activating cell death using Nutlin-3A (to activate P53 through inhibition of MDM2) or S63845 (to inhibit the pro-survival BCL-2 protein MCL-1), we have identified genes that are necessary for the apoptotic process to occur. One such gene, found using both screening methodologies, is Arrestin domain-containing 3 (ARRDC3). ARRDC3 is a poorly studied gene, but the best-known functionality for other arrestin family genes is involvement in G-protein coupled receptor ubiquitination and degradation. We are aiming to elucidate the function of ARRDC3 in organismal development and apoptosis, and identify whether it has potential as a drug target for cancer therapy.