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Knowledge about Solanaceae species naturally adapted to salinity is scarce, despite the fact that a considerable number of Solanaceae has been reported growing in saline environments. Lycium humile Phil. inhabits extreme saline soils in the Altiplano-Puna region (Central Andes, South America) and represents a promising experimental model to study salt tolerance in Solanaceae plants. Seeds, leaves and roots were collected from a saline environment (Salar del Diablo, Argentina). Seeds were scarified and 30 days after germination salt treatments were applied by adding NaCl salt pulses (up to 750 or 1000 mM). Different growth parameters were evaluated, and leaf spectral reflectance, endogenous phytohormone levels, antioxidant capacity, proline and elemental content, and morpho-anatomical characteristics in L. humile under salinity were analyzed both in controlled and natural conditions. The multiple salt tolerance mechanisms found in this species are mainly the accumulation of the phytohormone abscisic acid, the increase of the antioxidant capacity and proline content, together with the development of a large leaf water-storage parenchyma that allows Na+ accumulation and an efficient osmotic adjustment. Lycium humile is probably one of the most salt-tolerant Solanaceae species in the world, and, in controlled conditions, can effectively grow at high NaCl concentrations (at least, up to 750 mM NaCl) but also, in the absence of salts in the medium. Therefore, we propose that natural distribution of L. humile is more related to water availability, as a limiting factor of growth in Altiplano-Puna saline habitats, than to high salt concentrations in the soils. [Display omitted] • Lycium humile probably is one of the most salt-tolerant Solanaceae species. • Lycium humile can grow at high salt concentrations (at least, up to 750 mM NaCl). • Antioxidant capacity, abscisic acid and proline convey salt tolerance. • Large leaf water-storage parenchyma allows Na+ accumulation and osmotic adjustment. [ABSTRACT FROM AUTHOR]