PRDM15, a transcriptional regulator belonging to the PRDM family, has significant roles in multiple biological processes. It is involved in pathways like DNA damage repair, cell metabolism regulation, and is crucial for maintaining naive pluripotency, with its dysregulation often associated with various diseases [1,2,5]. Genetic models, such as knockout (KO) mouse models, are valuable tools for studying its functions.

In colorectal cancer, knockdown of PRDM15 inhibits DNA damage repair and increases radiosensitivity, as it promotes DNA repair by interacting with the DNA-PKcs and Ku70/Ku80 complex [1]. In B-cell lymphomas, abrogation of PRDM15 in KO models leads to a metabolic crisis and selective death of lymphoma cells, indicating its role in fueling the metabolic requirements of these cells [2]. In holoprosencephaly, genetic deletion of murine Prdm15 causes anterior/posterior (A/P) patterning defects and brain malformations, and in Xenopus laevis, morpholino-mediated knockdown of Prdm15 recapitulates anterior neural features seen in related syndromes [3,4].

In conclusion, PRDM15 is essential in regulating DNA damage repair, cell metabolism, and embryonic development. The use of KO mouse models and other loss-of-function experiments has revealed its significance in diseases like colorectal cancer, B-cell lymphomas, and syndromes related to holoprosencephaly, providing insights into potential therapeutic targets for these conditions.