Updated project metadata. Sex-dependent differences in kidney function have been recognized. However, the molecular mechanisms underlying these differences remain largely unexplored. Advances in genomics and proteomic technologies now allow for an extensive characterization of sex differences. In this study, the authors apply multi-omics approaches integrating RNA-seq, ATAC-seq, and proteomics to investigate gene expression, chromatin accessibility, and protein expression between male and female mouse proximal tubules. This study identifies a large number of sex-biased genes and proteins associated with various kidney functions, including metabolism and transport processes. The authors demonstrate that sex differences may also arise from differences in interaction between transcription factors and accessible chromatin regions. A comprehensive web resource is provided to the research community to advance understanding of sex differences.