Due to their immobility, plants cannot escape unfavorable conditions. Probably because of this, they have evolved intrinsic molecular mechanisms that allow fine-tuning of cell division with developmental programs and environmental conditions. Research in Arabidopsis thaliana has implicated a role for the SIAMESE/SIAMESE-RELATED (SIM/SMR) gene family in these processes, encoding for plant-specific cell cycle inhibitors acting on cyclin-dependent kinase activity. However, currently any fundament knowledge on SIM/SMR genes in crop species is lacking, undoubtedly in part due to gene redundancy. Here, we aim to overcome this redundancy in maize by using BREEDIT technology that makes use of multiplex CRISPR/Cas9 technology in combination with classical breeding to combine traits. Using this technology, we will generate on basis of co-expression data a collection of 100 maize genotypes randomly differing in SIM/SMR knockout combinations. Subsequently, these lines will be phenotypically screened under mild drought and DNA damage-inducing conditions. Additionally, being a pivotal part for feed and human diet, kernels will be quantitatively and qualitatively characterized. Combined, the data obtained should not only represent a pioneering phenotypic characterization of the SIM/SMR gene family in a crop species but might as well address the question of whether SIM/SMR genes represent attractive targets for engineering of climate-resilient plants.