The article discusses the context-dependent control of alternative splicing by RNA-binding proteins (RBPs). Alternative splicing, a process where pre-mRNA transcripts are processed to produce different mRNA isoforms, is regulated by multiple RBPs, which create a distribution of alternatively spliced products in a given cell type. The authors highlight the complex and combinatorial nature of splicing regulation, where the same genomic sequences can be recognized differently by RBPs in different cell types. They emphasize the importance of understanding the regulatory landscape, including cis-acting RNA elements and trans-acting factors, and the role of RBPs in modulating splice site selection and pairing. The article also explores the cooperative and competitive interactions between RBPs, the tissue specificity of splicing regulation, and the impact of signaling events on splicing. Finally, it outlines future directions for research, including the need for global analyses to establish regulatory principles and the integration of functional genomics and biochemistry to understand splicing regulation in detail.The article discusses the context-dependent control of alternative splicing by RNA-binding proteins (RBPs). Alternative splicing, a process where pre-mRNA transcripts are processed to produce different mRNA isoforms, is regulated by multiple RBPs, which create a distribution of alternatively spliced products in a given cell type. The authors highlight the complex and combinatorial nature of splicing regulation, where the same genomic sequences can be recognized differently by RBPs in different cell types. They emphasize the importance of understanding the regulatory landscape, including cis-acting RNA elements and trans-acting factors, and the role of RBPs in modulating splice site selection and pairing. The article also explores the cooperative and competitive interactions between RBPs, the tissue specificity of splicing regulation, and the impact of signaling events on splicing. Finally, it outlines future directions for research, including the need for global analyses to establish regulatory principles and the integration of functional genomics and biochemistry to understand splicing regulation in detail.