Higher plants evolved multiple innate immune systems to combat pathogens present in their living environment. However, activation of the complex immune responses allocates nutrient resources into biosynthesis of various defense molecules, and this in turn often represses growth and development of the entire plant. Over the years, the significance of the effective co-regulation of growth and immunity has been demonstrated with dwarf phenotypes of autoimmune mutant lines of model plants displaying constitutive defense responses (van Wersch et al., 2016van Wersch R. Li X. Zhang Y. Mighty dwarfs: Arabidopsis autoimmune mutants and their usages in genetic dissection of plant immunity.Front. Plant Sci. 2016; 7: 1717Crossref PubMed Scopus (57) Google Scholar). This tightly regulated balance, termed the growth-immunity trade-off, is an important objective in plant breeding, which ultimately aims at plant cultivars that are both highly resistant and efficient in terms of growth and yield (Ning et al., 2017Ning Y. Liu W. Wang G.-L. Balancing immunity and yield in crop plants.Trends Plant Sci. 2017; 22: 1069-1079Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar). The molecular mechanisms controlling this trade-off involve a vast number of different factors, including plant hormones. Among these, the defense hormone salicylic acid (SA) that controls the systemic acquired resistance (SAR), a broad-spectrum disease resistance triggered in uninfected tissues in response to a local infection, has been proposed as an important player in the balance between growth and immunity (Figure 1) (van Butselaar and van den Ackerveken, 2020van Butselaar T. van den Ackerveken G. Salicylic acid steers the growth–immunity tradeoff.Trends Plant Sci. 2020; 25: 566-576Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar). Notably, SA is not the only small molecule involved in controlling SAR. Recently, N-hydroxy-pipecolic acid (NHP), a non-protein amino acid derived from lysine upon pathogen infection, has been shown to constitute another key signal required to initiate SAR in the model plant Arabidopsis thaliana (Chen et al., 2018Chen Y.-C. Holmes E.C. Rajniak J. Kim J.-G. Tang S. Fischer C.R. Mudgett M.B. Sattely E.S. N-Hydroxy-pipecolic acid is a mobile metabolite that induces systemic disease resistance in Arabidopsis.Proc. Natl. Acad. Sci. U S A. 2018; 115: E4920-E4929Crossref PubMed Scopus (107) Google Scholar; Hartmann et al., 2018Hartmann M. Zeier T. Bernsdorff F. Reichel-Deland V. Kim D. Hohmann M. Scholten N. Schuck S. Bräutigam A. Hölzel T. et al.Flavin monooxygenase-generated N-hydroxypipecolic acid is a critical element of plant systemic immunity.Cell. 2018; 173: 456-469Abstract Full Text Full Text PDF PubMed Scopus (157) Google Scholar). NHP biosynthesis has been shown to be widely conserved across the plant kingdom and activated in response to bacterial infection in tissues of a few investigated plant species, but the requirement of NHP for immunity and for SAR response in species other than Arabidopsis has been so far not unequivocally proved. However, it has been shown that transient local expression of NHP biosynthetic genes can trigger SAR in tomato (Holmes et al., 2019Holmes E.C. Chen Y.C. Sattely E.S. Mudgett M.B. An engineered pathway for N-hydroxy-pipecolic acid synthesis enhances systemic acquired resistance in tomato.Sci. Signal. 2019; 12: eaay3066Crossref PubMed Scopus (25) Google Scholar). Activity of plant signaling and defense molecules can be controlled by glycosylation, which may alter their hydrophilicity, stability, chemical properties, and subcellular localization. The glycosylation process is mediated by UDP-glycosyltransferases (UGTs), enzymes transferring nucleotide-diphosphate-activated sugars to low-molecular-weight aglycone substrates. For instance, in plants under pathogen attack, accumulating SA can be modified to its inactive derivatives, including SA glucose ester and SA β-glucoside. According with published result, these conjugates are formed by UGT74F1 and UGT74F2 with a contribution from UGT76B1, which can additionally attach glucose to isoleucic acid (Figure 1) (Noutoshi et al., 2012Noutoshi Y. Okazaki M. Kida T. Nishina Y. Morishita Y. Ogawa T. Suzuki H. Shibata D. Jikumaru Y. Hanada A. et al.Novel plant immune-priming compounds identified via high-throughput chemical screening target salicylic acid glucosyltransferases in Arabidopsis.Plant Cell. 2012; 24: 3795-3804Crossref PubMed Scopus (114) Google Scholar; von Saint Paul et al., 2011von Saint Paul V. Zhang W. Kanawati B. Geist B. Faus-Keßler T. Schmitt-Kopplin P. Schäffner A.R. The Arabidopsis glucosyltransferase UGT76B1 conjugates isoleucic acid and modulates plant defense and senescence.Plant Cell. 2011; 23: 4124-4145Crossref PubMed Scopus (119) Google Scholar). Notably, NHP has been also detected as O-glucosylated conjugate (NHPG) in Arabidopsis seedlings upon pathogen infection, suggesting that activity of this signaling molecule can be as well controlled by sugar substitution (Chen et al., 2018Chen Y.-C. Holmes E.C. Rajniak J. Kim J.-G. Tang S. Fischer C.R. Mudgett M.B. Sattely E.S. N-Hydroxy-pipecolic acid is a mobile metabolite that induces systemic disease resistance in Arabidopsis.Proc. Natl. Acad. Sci. U S A. 2018; 115: E4920-E4929Crossref PubMed Scopus (107) Google Scholar). In a recent study, Cai et al., 2021Cai J. Jozwiak A. Holoidovsky L. Meijler M.M. Meir S. Rogachev I. Aharoni A. Glycosylation of N-hydroxy-pipecolic acid equilibrates between systemic acquired resistance response and plant growth.Mol. Plant. 2021; 14: 440-455Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar identified UGT76B1 as the enzyme responsible for NHP glucosylation. Selection of UGT76B1 as a candidate protein was based on gene co-expression analysis and its function in NHP substitution has been supported by transient expression in Nicotiana benthamiana and in vitro enzymatic assays with recombinant proteins produced in yeast and bacterial heterologous systems. These analyses provided clear evidence that, in addition to previously reported SA conversion, UGT76B1 also possesses NHP-UGT activity, yet shows different enzyme kinetics toward both substrates. Function of UGT76B1 in NHP substitution in planta has been further supported with metabolic analysis of Arabidopsis loss-of-function ugt76b1 and UGT76B1 overexpression ( OE ) lines. Furthermore, phenotypic analysis revealed that ugt76b1 knockout overaccumulating NHP in leaves shows a dwarf and early senescence phenotype that correlates with constitutive defense responses, including elevated local and systemic resistance. On the contrary, displaying higher levels of NHPG, UGT76B1-OE plants exhibit enlarged rosettes and delayed leaf senescence, and are more prone to pathogen infection as compared with wild-type plants (Figure 1). Of note, parallel studies revealed ugt76b1 growth and immune phenotypes can be reverted by a mutation in flavin-dependent monooxygenase 1 (FMO1) that is required for NHP biosynthesis, suggesting that, among the reported UGT76B1 substrates, NHP has the strongest contribution to the disturbance of growth-immunity balance observed in ugt76b1 plants (Bauer et al., 2021Bauer S. Mekonnen D.W. Hartmann M. Yildiz I. Janowski R. Lange B. Geist B. Zeier J. Schäffner A.R. UGT76B1, a promiscuous hub of small molecule-based immune signaling, glucosylates N-hydroxypipecolic acid and balances plant immunity.Plant Cell. 2021; https://doi.org/10.1093/plcell/koaa044Crossref Scopus (10) Google Scholar; Mohnike et al., 2021Mohnike L. Rekhter D. Huang W. Feussner K. Tian H. Herrfurth C. Zhang Y. Feussner I. The glycosyltransferase UGT76B1 modulates N-hydroxy-pipecolic acid homeostasis and plant immunity.Plant Cell. 2021; https://doi.org/10.1093/plcell/koaa045Crossref PubMed Scopus (18) Google Scholar). Based on their results, Cai et al., 2021Cai J. Jozwiak A. Holoidovsky L. Meijler M.M. Meir S. Rogachev I. Aharoni A. Glycosylation of N-hydroxy-pipecolic acid equilibrates between systemic acquired resistance response and plant growth.Mol. Plant. 2021; 14: 440-455Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar come up with a working model underlying the importance of UGT76B1 in the growth-immunity trade-off. They proposed that, under normal conditions, only trace amounts of NHP are produced and rather immediately converted to the inactive NHPG. Pathogen recognition activates NHP biosynthesis and accumulation, primarily at the side of pathogen attack. NHP is further transported to distant tissues to initiate the SAR response, which is accompanied with growth inhibition and eventually early senescence. However, at a certain NHP threshold level UGT76B1 is activated to decline NHP activity and attenuate the SAR response, which in turn releases plant growth and delays senescence (Figure 1). This model suggests that precise manipulation of genes involved in NHP biosynthesis and modification may constitute a promising approach to engineer plants with desired balance between growth and immunity. So far, enhanced NHP accumulation upon pathogen recognition has been observed in seedlings of tomato, N. benthamiana, and Brassica rapa, but not in soybean and corn. However, NHPG has been detected only in Arabidopsis and in B. rapa, suggesting that the production of this NHP conjugate may be restricted to the Brassicaceae family (Holmes et al., 2019Holmes E.C. Chen Y.C. Sattely E.S. Mudgett M.B. An engineered pathway for N-hydroxy-pipecolic acid synthesis enhances systemic acquired resistance in tomato.Sci. Signal. 2019; 12: eaay3066Crossref PubMed Scopus (25) Google Scholar). On the other hand, genetic manipulation in tomato and in N. benthamiana indicated that engineered NHP biosynthesis combined with UGT76B1-mediated glucosylation can be used to control defense responses in these species (Holmes et al., 2019Holmes E.C. Chen Y.C. Sattely E.S. Mudgett M.B. An engineered pathway for N-hydroxy-pipecolic acid synthesis enhances systemic acquired resistance in tomato.Sci. Signal. 2019; 12: eaay3066Crossref PubMed Scopus (25) Google Scholar, Holmes et al., 2021Holmes E.C. Chen Y.-C. Mudgett M.B. Sattely E.S. Arabidopsis UGT76B1 glycosylates N-hydroxy-pipecolic acid and inactivates systemic acquired resistance in tomato.Plant Cell. 2021; https://doi.org/10.1093/plcell/koaa052Crossref PubMed Scopus (16) Google Scholar; Cai et al., 2021Cai J. Jozwiak A. Holoidovsky L. Meijler M.M. Meir S. Rogachev I. Aharoni A. Glycosylation of N-hydroxy-pipecolic acid equilibrates between systemic acquired resistance response and plant growth.Mol. Plant. 2021; 14: 440-455Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar). Collectively, these studies indicate that NHP biosynthesis combined with UGT76B1 activity may have a potential in rational control of the growth-immunity trade-off in crop plants. No conflict of interest declared.