Schreier , Tina B.Balahadia, Christian PaoloDanila, Florence R.2026-01-302026-01-300022-0957ORCID:/0009-0006-8536-6010/work/203697441ORCID:/0000-0002-7352-3852/work/203701922https://hdl.handle.net/1885/733805074Boosting crop productivity while enhancing resilience to climate change and disease remains a major challenge. Plasmodesmata (PD), which mediate cell-to-cell connectivity, are crucial for plant growth but remain underutilized as targets for crop improvement. This review focuses on C4 photosynthesis to demonstrate the importance of enhanced cell-to-cell connectivity to improve productivity. In C4 plants, connectivity between mesophyll (M) and bundle sheath (BS) cells is essential for building an efficient CO2-concentrating mechanism. Enhanced PD frequency at the M–BS interface is a key feature of C4 Kranz leaf anatomy, and thus an important trait to introduce in engineering C4 photosynthesis into C3 crops. We propose potential gene targets to engineer PD connectivity, while emphasizing the need for further research to discover new targets that affect PD formation and regulation. We also discuss advances in biotechnological tools that are important for both molecular studies and deploying strategies to manipulate PD in crops. These target genes and tools may ultimately unlock new capabilities to improve crop productivity and resilience by engineering cell-to-cell connectivity within various tissues.TBS was supported by a Biotechnology and Biological Sciences Research Council (BBSRC) Discovery Fellowship (grant ref.: BB/X010015/1), the John Fell Oxford University Press Research Fund, and the Gatsby Charitable Foundation. CPB was supported by an international scholarship from The Australian National University Research School of Biology. FRD was supported by a Thomas Davies Grant from the Australian Academy of Science and a seed funding grant from The Australian National University Research School of Biology.17en© 2025 The AuthorsC4 photosynthesisCO2-concentrating mechanismcrop improvementmesophyll-bundle sheath cell interfaceplasmodesmatasymplastic transport2025-11-1110.1093/jxb/eraf497105028596503