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) we have identified Arrestin domain-containing 3 (ARRDC3) as being necessary for proper P53-driven apoptosis to occur. We have further characterised the role of ARRDC3 within apoptosis, and have also looked more broadly at how ARRDC3 is necessary for organismal development using a mouse model. Moving forward, we aim to examine the proteome surrounding ARRDC3, and elucidate whether potential physical interactions with MDM2 and P53 might be driving its role in apoptosis.