Thirty years of plant farnesylation research: Few substrates, many gaps, and a clear path forward

Protein farnesylation - the covalent attachment of a 15-carbon farnesyl isoprenoid to a C-terminal CaaX motif by protein farnesyltransferase (PFT, FTase) - is one of the most functionally important post-translational modifications in eukaryotic biology. In mammals, the biomedical significance of farnesylation is well established. The FTase inhibitor (FTI) lonafarnib treats Hutchinson-Gilford progeria syndrome. FTase remains an oncology target, and chemical proteomic strategies have mapped more than 100 farnesylated substrates at single-protein resolution. In plants, genetic evidence establishes that FTase governs abscisic acid (ABA) signalling, brassinosteroid (BR) homeostasis, cytokinin (CK) partitioning, meristem development, thermotolerance, innate immunity, nitrogen sensing, and drought resilience across Arabidopsis thaliana, barley (Hordeum vulgare), canola (Brassica napus), wheat (Triticum aestivum), soybean (Glycine max), and rice (Oryza sativa). Yet fewer than fifteen substrates have been biochemically confirmed in any plant species after nearly three decades of research, and no crop species has been subjected to prenylome-scale chemical proteomics. This review synthesizes the plant and animal farnesylation literature and argues that this disconnect is methodological rather than biological. We trace the arc from FTase enzymology through the emerging catalogue of confirmed plant substrates, exemplified by the HSP40 co-chaperones J2/J3, the cytokinin-biosynthetic enzyme AtIPT3, and plasmodesmal HIPPs, to crop engineering outcomes. We propose a spatial-switch model to organize the confirmed substrate data into a unifying mechanistic framework, while acknowledging that this model awaits systematic experimental testing. Finally, we outline the chemical biology tools - alkyne-isoprenoid probes, quantitative prenylomics profiling - that must be adapted for plant systems to close the gap between substrate prediction and biochemical validation. Farnesylation exemplifies how a conserved eukaryotic modification can be harnessed for crop improvement once the underlying substrate biology is sufficiently understood.