Sheldon Penman’s work spanned the intersection of biochemistry and structural biophysics. He revealed the organization and assembly of regulatory complexes in nuclear microenvironments; studied compartmentalization in the cytoplasm and rRNA biosynthesis; and uncovered RNA’s role in the architectural organization of transcriptional regulatory machinery and of nuclear structure and function. He was an exceptional mentor, and many of his students have gone on to make pivotal contributions in science.