p300 and CBP are paralogous transcriptional co-activators and lysine acetyltransferases and are often abbreviated to p300/CBP owing to their functional overlap. Underlying their importance, mutations in EP300 or CREBBP have been observed in several cancer types and are present in the developmental disorder, Rubinstein-Taybi Syndrome. To investigate redundant and specific roles of p300 and CBP, we have generated Ep300-FKBP12F36V and Crebbp-FKBP12F36V mice. These models facilitate the rapid degradation of p300 or CBP allowing the primary effects of losing either protein to be investigated. Using these models, we aim to tease apart the relative contribution of p300 and CBP to nascent transcription and the deposition of acetylation. Importantly, p300 and CBP are potential therapeutic targets in a variety of human cancers with many ongoing efforts to pharmacologically target them, including with PROTACs. In our ongoing work we aim to gain a better understanding of the functional redundancies and differences between p300 and CBP, with potential implications for basic and translational biology.