From Nitrate Perception to Environmental Adaptation: Functional Elucidation and Regulatory Networks of the Plant NLP Family

Nitrogen is a necessary macronutrient that limits plant growth and crop productivity, yet excessive fertilizer application has resulted in serious environmental consequences. The NIN-like protein (NLP) family consists of plant-specific transcription factors that serve as central regulators of nitrate signaling. In 2022, the discovery of NLP7 as an intracellular nitrate receptor represented a major conceptual shift from transcriptional regulation to signal perception. This review systematically summarizes the molecular architecture of NLP proteins, focusing on the conserved RWP-RK DNA-binding domain, the PB1 protein-protein interaction module, and the GAF-like domain associated with the integration of multiple signals. It also examines the species-specific expansion and evolutionary diversification of the NLP family, as well as the multilayered mechanisms that regulate NLP activity, including phosphorylation as a signal-dependent molecular switch, SUMOylation as a negative feedback mechanism, transcriptional regulation of downstream targets, and PB1-mediated protein interaction networks. In addition to nitrate signaling, NLPs serve as central hubs linking nitrogen and carbon metabolism and mediating responses to abiotic stresses including cold, heat, salinity, and iron deficiency. Notably, the NLP7–NIGT1.3 module coordinates a growth–stress trade-off during iron deficiency by modulating nitrate signaling intensity, revealing a previously unrecognized mechanism for balancing stress adaptation with growth maintenance. NLPs also participate in developmental processes, including lateral root formation and symbiotic nodulation. Finally, this review highlights the potential of NLP-based approaches for crop genetic improvement, such as overexpression of key NLP genes or CRISPR/Cas-mediated editing, to improve nitrogen use efficiency, stress tolerance, and yield. Collectively, these insights provide a theoretical foundation for developing crop varieties with improved nitrogen-use efficiency and context-dependent stress adaptation, while acknowledging the inherent trade-offs between productivity and resilience.