The non-canonical (BRG1/BRM-Associated Factor) BAF complex is one of the final assembly forms of the major class of ATP-dependent SWI/SNF chromatin remodeling complexes which are large multi-subunit complexes that play a crucial role in the dynamic regulation of the chromatin architecture and DNA accessibility in eukaryotic cells [1, 2]. Recent studies revealed the high prevalent mutational frequency in genes encoding for SWI/SNF subunits in over 20% of human cancers leading to perturbations in the complex formation and function and providing strong support for their driving role in oncogenesis [3, 4, 5]. The non-canonical BAF complex was identified as a vulnerable target in several BAF-related cancer types as it seems to maintain the oncogenic gene expression at retained mSWI/ SNF sites [6, 7]. In particular, the complex-specific subunits (Bromodomain-containing protein 9) BRD9, GLTSCR1 (glioma tumor suppressor candidate region gene 1) and its paralog GLTSCR1L (GLTSCR1- like) are suggested to intake an essential role in the complex functional assembly [8, 9]. The underlying structural mechanisms and crucial interaction sites within the subunits contributing to the complex organization and function in the cell remain unknown. The aim of the proposed project is to reveal the molecular basis for the interactions between the specific subunits of the non-canonical BAF complex that might shed light on its biological role. First, we will identify the minimal interaction regions within the individual proteins and then perform their detailed structural characterization. Our goal is to construct a detailed structural map of the human non-canonical BAF complex that will reliably predict its behavior under pathological conditions. We will use structural and biophysical methods not only for detailed structural characterization of the interaction network within the complex, but also for validation of results in cells. Clarification of the structural relationships between the individual subunits and their interaction properties under normal and pathological conditions will lead to a better understanding of the regulation and function of the non-canonical BAF complex at the molecular level and will help to design new therapeutic approaches.